Advances in understanding the role of interleukins in pulmonary fibrosis (Review)
- Authors:
- Published online on: November 28, 2024 https://doi.org/10.3892/etm.2024.12775
- Article Number: 25
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Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Abstract
1. Introduction
Pulmonary fibrosis (PF) is a severe and irreversible consequence of various respiratory diseases, such as alveolitis and interstitial pneumonitis, which is characterized by excessive accumulation of extracellular matrix (ECM) and fibroblast proliferation (1). These pathological processes are accompanied by inflammatory responses and significant damage to the lung architecture (2,3). Subsequent to the injury of alveolar epithelial cells (AECs), multiple interconnected downstream profibrotic pathways are activated, and subsequent aberrant repair mechanisms can lead to harmful scarring in pulmonary tissues and severe impairment of lung function (4,5). Inflammatory responses (6), oxidative stress (7,8) and apoptosis (9) have been reported as possible pathological mechanisms underlying PF.
Globally, the number of patients with PF is increasing, which may be related to aging, increased awareness of the disease as well as improved diagnostic techniques and tools (10,11). The estimated incidence and prevalence of PF are 0.09-1.30/10,000 patients and 0.33-4.51/10,000 patients, respectively (12). Despite recent advances in the treatment of PF, the disease shows a poor prognosis and current available therapeutic options can only slow its progression (13).
Various cytokines have been implicated in the occurrence and development of PF (14), among which interleukins (ILs) have been extensively reported and are considered to be associated with PF (15,16). ILs are a type of proteins that promote interactions with immune and non-immune cells, and are essential in the activation, proliferation, migration and adhesion of immune cells (17). ILs were previously considered to be produced exclusively by leukocytes. However, monocytes, endothelial cells, macrophages, dendritic cells and T cells also express ILs (18,19). ILs can modulate cell proliferation, differentiation, and the initiation of inflammatory and immunological responses (20,21). They also exert autocrine and paracrine effects (22). ILs have been identified as significant contributors to the pathology of PF (16,23). The present study reviews the current research on ILs in PF and summarizes the roles and mechanisms of ILs associated with PF.
2. Interleukins associated with PF
ILs belong to a large family that can be subdivided into numerous types and are critical mediators of PF pathogenesis (14). Recent studies have demonstrated that ILs contribute to PF development by modulating various biological processes, including inflammation (24,25), immune responses (26), autophagy (27), cellular senescence (28) and epithelial-mesenchymal transition (EMT) (29,30), as illustrated in Fig. 1. Notably, different types of ILs exert disparate effects on PF, as subsequently discussed in the present review.
ILs that promote PF. IL-1
IL-1, also termed lymphocyte-stimulating factor, belongs to the IL-1 family (31). IL-1 locally regulates immunity, promoting B lymphocyte proliferation and antibody production (32). In addition, IL-1 can also regulate the inflammatory response, which may cause fever, pyogenic arthritis, pyoderma gangrenosum, acne and Schnitzler syndrome (33).
There are two subtypes of IL-1: i) IL-1α; and ii) IL-1β (31). IL-1α can be synthesized by hematopoietic and non-hematopoietic cell types, whereas IL-1β is synthesized primarily by mononuclear phagocytes (34). IL-1α promotes the conversion of fibroblasts into proinflammatory phenotypes, and IL-1β initiates the recruitment of neutrophils and lymphocytes, resulting in inflammation and lung fibrosis at the site of injury (34). It has been demonstrated that the molecular mechanism of lung fibrosis progression is improved by regulating the secretion of inflammatory factors such as IL-1β in lung tissue (25), and that the inhibition of IL-1 expression in lung fibrosis-related diseases can attenuate fibrosis, indicating that IL-1 is a key target in PF (24). IL-1R1 is a potential therapeutic target for the treatment of chronic obstructive pulmonary disease (COPD), and a relevant clinical trial has validated that monoclonal antibodies selectively bind to the receptor IL-1R1 and suppress the activation of IL-1α and IL-1β, and it can improve lung function as well as the quality of patients' lives (35). A recent study revealed that the combined inhibition of IL-1, IL-33 and IL-36 signaling by targeting the IL-1 receptor accessory protein could ameliorate lung fibrosis in preclinical models (36). Notably, this human phase I clinical trial concerning the anti-IL1RP antibody is currently ongoing (36), suggesting a promising method for treating PF in future clinical practice.
IL-6. IL-6 is a key cytokine in the acute-phase response and participates in the pathogenesis of a number of chronic inflammatory diseases including cancer (37-39). Monocytes and lymphocytes are the primary sources of IL-6(40). In the early wound healing stage, M1 macrophages, lymphocytes and neutrophils infiltrate and play a pivotal role in wound healing by secreting various factors, including TNF-α and IL-6(41). In the inflammation-terminating stage of injury repair, M2 macrophages regulate the inflammatory response and secrete TGF-β1 and platelet-derived growth factor to promote fibroblast proliferation, resulting in remodeling of the ECM and excessive deposition of collagen (42).
IL-6 can stimulate fibrosis by initiating chronic inflammation and activating the TGF-β pathway (43), whereas TGF-β1 is at present, the most potent profibrotic cytokine (44). In bleomycin (BLM)-induced mice with PF, the expression of fibrosis-related cytokine IL-6 and myofibroblast marker collagen type I in the lymphoid fibroblast supernatant, serum, blood and bronchoalveolar lavage fluid induced by TGF-β1 were significantly increased (45).
IL-6 promotes PF as a multifunctional cytokine involved in the inflammatory response and fibrosis. IL-6 induces the maturation of T and B lymphocytes and participates in acute inflammatory responses (46). IL-6 also induces collagen deposition and ECM accumulation and stimulates fibroblast proliferation, thereby promoting the development of fibrosis (45). Clinical studies demonstrated an association between serum IL-6 levels and lung function impairment in patients with PF (47,48). The detection of serum IL-6 levels in patients with PF could provide a basis for the clinical judgment of respiratory function (47). Moreover, results of a phase III clinical trial of an IL-6 receptor antagonist has indicated that IL-6 is a driver of PF, and inhibition of IL-6 could help restore lung function (49). To the best of our knowledge, there are no clinical studies that directly focus on IL-6 and PF, but the aforementioned findings indicate that targeting IL-6 may be a promising therapeutic approach against PF.
IL-8. IL-8, also termed chemokine CXCL8, is expressed during inflammation, tumors and allergies (50). IL-8 is involved in cellular immunity and delayed-type hypersensitivity inflammation, and its main biological roles include chemotaxis and activation of neutrophils, promotion of lysosomal enzyme activity and phagocytosis of neutrophils, mediation of cytotoxicity, and local inflammation-related immune responses to assist antibody production (51,52). Papiris et al (53) found that the amount of IL-8-secreting alveolar macrophages increases in patients with fibrosing alveolitis and that elevated levels of IL-6 and IL-8 are characteristics of early PF (43).
Fibrotic mesenchymal progenitor cells (MPCs) in lung tissue are the original cells of PF fibroblasts (43). IL-8 derived from MPCs facilitates the proliferation, differentiation and migration of MPCs and induces macrophage migration to fibroblast foci via the receptor CXCR1/2(54). Li et al (55) demonstrated that IL-8 production is induced in airway epithelial cells through the NF-κB pathway, and the induced IL-8 expression is not only involved in neutrophil recruitment in airway inflammation in lung diseases, but also associated with airway fibrosis and remodeling by provoking the proliferation and migration of lung fibroblasts and mesenchymal stem cells.
IL-13. IL-13 is produced mainly by Th2 lymphocytes, epithelial cells, and macrophages (56). IL-13 is functionally similar to IL-4 because their amino acid sequences share 20-25% homology (57). IL-13 is a proinflammatory cytokine and its role in allergic inflammation, asthma and inflammatory bowel disease has been well documented (58-60). IL-13 stimulates fibroblast activation and proliferation, increases smooth muscle cell contraction and ECM deposition, and facilitates mucus production (26,61). In addition, IL-13 can induce the production of profibrotic cytokines (such as TGF-β, PDGF, connective tissue growth factor and collagen type I) and fibronectin production (62). Clinical trials have confirmed that in patients with COPD and type 2 inflammation, dupilumab, which blocks both IL-4 and IL-13, showed improved lung function compared with patients treated with placebo (61,63). However, in patients with PF, blocking IL-13 did not achieve a satisfactory therapeutic effect (64), hence, the clinical role of IL-13 inhibitors in the treatment of PF still needs to be further studied.
IL-17. IL-17 is a proinflammatory cytokine involved in chronic inflammation that occurs in the pathogenesis of allergies, malignancies and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and psoriasis (65). IL-17 regulates immune function by inducing the secretion of anti-inflammatory molecules such as cytokines, anti-pathogenic peptides and chemokines (66). IL-17 can act on a variety of cellular targets. For example, it induces inflammation when acting on endothelial cells (67) and induces cytokine and enzyme production when acting on epithelial cells and fibroblasts (68,69). In addition, IL-17 induces inflammation by increasing the production of proinflammatory cytokines when acting on monocytes and dendritic cells (70).
The main subtypes of the IL-17 family are IL-17A to IL-17F, which bind to the IL-17 receptor (IL-17R) complex and consist of two chains: i) IL-17RA; and ii) IL-17RC (71). IL-17RA is expressed in almost every cell type, including epithelial and endothelial cells and fibroblasts (72,73). IL-17A expression levels are positively correlated with inflammation scores of skin and lung as well as skin fibrosis in PF mice and IL-17A inhibits autophagy in AECs (69). IL-17RC acts on numerous cell types, including CD4+ T cells, macrophages and neutrophils, and plays important roles in lung inflammation (74-76). IL-17E, often referred to as IL-25, is secreted by T2, epithelial, endothelial and T cells, alveolar macrophages, eosinophils and basophils, all of which are closely associated with the inflammatory response (77). In lung tissues from patients with PF, the levels of IL-17E and its receptor IL-17RB are increased, suggesting that they drive PF by mediating EMT in AECs and by recruiting and activating lung fibroblasts (29,30).
IL-18. IL-18 regulates innate and adaptive immunity (78). As a proinflammatory cytokine, IL-18 promotes the type I response and secretes inflammatory factors such as IL-1β and TNF-α, which exacerbates lung tissue injury at an early stage (79). Under the stimulation of IL-10, IL-18 induces the polarization of M2 macrophages (80). Notably, polarized M2 macrophages secrete TGF-β1(81), which is the primary idiopathic dominant factor in ECM overproduction and deposition, fibroblast proliferation and differentiation into fibroblasts in PF (82). Zhang et al (28) found that IL-18 promotes lung fibroblast senescence and the senescence-associated secretory phenotype of fibroblasts by downregulating Klotho expression. IL-18 promotes inflammation, cell differentiation and cytokine production by regulating multiple cell signaling pathways (83). For example, IL-18 induces the expression of intercellular adhesion factor ICAM-1, promotes inflammatory cell recruitment, and upregulates the expression and activity of NF-κB, which is involved in the early stage of lung injury in lung fibrosis models and is associated with the modulation of the expression of multiple cytokines, including IL-1, IL-2, IL-6 and TNF-α (84).
IL-23. IL-23 is primarily produced by dendritic cells and macrophages (85). IL-17, IL-22 and IL-23 are significantly elevated in patients with combined lung cancer and PF, suggesting that IL-17, IL-22 and IL-23 are sensitive biomarkers for the early diagnosis of these diseases (86). Moreover, IL-23/Th17 cells are associated with the development of various inflammatory diseases, such as arthritis (87), psoriasis (88), inflammatory bowel disease (89) and asthma (90). Results of a paper published in 2021 suggested that IL-23 may be a new therapeutic strategy for acute exacerbations of PF (91), however, no clinical trials or research data are available to date.
IL-33. IL-33 expression is stimulated in non-lethal cell stretching, particularly in mechanosensitive cells such as fibroblasts (92). IL-33 drives disease pathology and promotes the reduction of inflammation under different inflammatory conditions and diseases (93,94). For example, a clinical trial has demonstrated that IL-33 plays a key role in the pathogenesis of atopic dermatitis (95), and monoclonal antibodies against IL-33 have been shown to reduce airway inflammation and associated tissue damage in a preclinical study (96). IL-33 promotes the polarization of M1 to M2 macrophages through IL-33/ST2 signaling, a pathological feature of PF (97). It has also been reported that IL-33 is expressed in the basal cells of the airway epithelium, endothelial cells and fibroblasts of the human lungs (98). Xiong et al (26) demonstrated that BLM induces IL-33 production in vivo, which triggers and promotes PF by activating macrophages and enhancing IL-13 and TGF-β production. Clinical trials have shown that neutralizing IL-33 has therapeutic and anti-inflammatory effects in lung diseases, including COPD and allergic asthma (99,100). At present, there are no clinical data on IL-33 inhibitors in the treatment of PF, and further research is needed for the confirmation of whether IL-33 could be targeted for treating PF.
IL-36. IL-36 is a new member of the IL-1 family (101). It includes three agonist proteins, IL-36α, IL-36β and IL-36γ, and the antagonist protein IL-36Ra (101). IL-36 is responsible for acute and chronic tissue inflammation in human diseases such as COPD, PF, asthma and arthritis (102). On the one hand, IL-36Ra antagonizes IL-36γ-mediated induction of NF-κB activation via IL-36R, and further inhibits inflammation in the lungs by suppressing massive accumulation of lung fibroblasts (103). On the other hand, IL-36 provokes the activation of macrophages, epithelial cells and keratinocytes to secrete inflammatory factors including IL-6, IL-1β, IL-12, IL-23 and TNF-α (104).
IL-36β activates M2 macrophages, and in bone marrow dendritic cells, IL-36 stimulation induces the production of proinflammatory cytokines (such as IL-1β, IL-6, IL-12, IL-23 and TNF) (105,106). The IL-36 receptor is expressed predominantly by initial CD4+ T cells, and promotes differentiation towards Th1 and Th17 cells, and facilitates their proliferation and inflammatory cytokine production (107).
ILs that inhibit PF. IL-10
IL-10, an inhibitory factor of human cytokine synthesis, is an anti-inflammatory cytokine (108,109). IL-10 is mainly produced by lymphocytes, macrophages and mast cells and has immunomodulatory effects such as the inhibition of monocytes/macrophages, Th1 cell function and enhancement of B lymphocyte function (110). IL-10 inhibits the expression of inflammatory factors, such as TNF-α, IL-6 and IL-1, through activating macrophages and can exert an immunostimulatory effect in numerous cell types (111).
IL-10 inhibits the activation, migration and adhesion of inflammatory cells by downregulating the expression of the major histocompatibility antigen II on the surface of monocytes, decreasing its antigen-presenting effect and downregulating the activity of T lymphocytes (112,113). At the same time, IL-10 can reduce inflammatory cytokines, such as IL-2, INF-γ, TNF-α and CSF-GM, and thus attenuate the inflammatory response (114). Moreover, IL-10 inhibits the expression of cytokines, such as TNF-α, IL-1β and IL-8, and the expression of adhesion molecules (115).
IL-12. IL-12 is derived primarily from activated macrophages (116). IL-12 enhances cellular immunity and modulates immune responses (117). Previous studies have shown that early intervention with IL-12 promotes anti-inflammatory, immunomodulatory and antifibrotic effects in animal models of PF (118-120). In addition, IL-12 is a potent inducer of IFN-γ and it attenuates BLM-induced PF by modulating IFN-γ production (121).
The Th1/Th2 imbalance is crucial in the pathogenesis of PF, with Th1-type cells represented by IFN-γ, which may promote the repair of normal tissue structures, and Th2-type cytokines represented by IL-4, which may cause excessive damage repair, ECM deposition and fibrosis (122). When the balance of Th1/Th2 type cytokines shifts towards Th2 type cytokines, it can lead to the development of fibrosis (123). IL-12 induces the proliferation and differentiation of Th1 cells to produce Th1-type cytokines, and inhibits the proliferation and differentiation of Th2 cells (124).
IL-27. IL-27 is a member of the cytokine IL-12 family, produced primarily by dendritic cells and macrophages, and it comprises the subunit proteins IL-27p28 and Epstein Bar virus-inducible protein 3(125). IL-27 is a multifunctional cytokine with anti-inflammatory and immunomodulatory properties (126). It has been suggested that IL-27 may play an antifibrotic role in lung fibroblast development, differentiation and collagen synthesis (127), and may alleviate TGF-β1-induced EMT in AECs (128). A recent study reported that IL-27 inhibits autophagy induced by the ERK/p38 signaling pathway and attenuates BLM-induced PF (129). Furthermore, mice deficient in IL-27RA show more severe collagen deposition in the lungs, suggesting that intact IL-27 signaling could limit PF progression (130).
IL-37. IL-37 was formerly defined as IL-1 family member 7, yet due to different functions from IL-1, it's now designated as an individual IL (22,131). IL-37 can either act directly inside the cell into the nucleus or be secreted outside the cell to act on its own membrane receptors or those of the surrounding cells to inhibit inflammation (132).
IL-37 and Smad3 are involved in the process of alveolitis and PF, and the IL-37b-Smad3 complex can suppress the phosphorylation of c-Jun N-terminal kinase and mitogen-activated protein kinase (MAPK), which is associated with IL-1-induced proinflammatory transcription factor AP-1(133). Inhibition of MAPK phosphorylation can downregulate the expression of Th2-type factors in peripheral blood mononuclear cells (133).
IL-38 is a potential inhibitor of IL-1 and the Toll-like receptor family with potent anti-inflammatory effects (134). The anti-inflammatory effects of IL-38 are related to the inhibition of inflammatory signaling pathways in target cells, suppression of T lymphocyte function and reduction in the secretion of inflammatory factors, including IL-6, TNF, CCL5 and CXCL10(135). IL-38 expression attenuates BLM-induced inflammatory and fibrotic injury in the lungs and reduces the production of proinflammatory and profibrotic cytokines (136).
Moreover, IL-38 has been reported to inhibit inflammatory processes by antagonizing IL-36R, similar to IL-36Ra or IL-1Ra (137). Furthermore, in a mouse model of BLM-induced PF, overexpression of IL-38 attenuated lung inflammation and fibrosis, reduced the production of inflammatory factors such as IL-1β, IL-6, IL-17A and TNF-α, and promoted the expression of the anti-inflammatory cytokine IL-1Ra (138).
ILs with dual effects on PF. IL-4
IL-4 is a pleiotropic cytokine that is primarily produced by activated T lymphocytes, mast cells, basophils and eosinophils cells (139). IL-4 exerts immunomodulatory effects on B lymphocytes, T and mast cells, macrophages and hematopoietic cells, and also exerts anti- and pro-inflammatory effects (61).
On the one hand, IL-4 attenuates PF by inhibiting macrophage infiltration, M2 polarization and collagen deposition, and the pharmacological treatment enhances IL-4-induced autophagy in macrophages and lung tissue in BLM-treated rats (27). On the other hand, IL-4 increases in the serum of patients with PF and in bronchoalveolar lavage fluid of mice after BLM intoxication (140). The primary role of IL-4 includes the induction of Th2 responses and the alternative activation of dendritic cell stimulation to present antigens to other immune cells and macrophages (141). In addition, the synergistic effect of IL-24 and IL-4 promotes M2-type polarization of macrophages, which further promotes the development of PF (140). However, M2 macrophages can have an anti-inflammatory and pro-wound healing phenotype; when this process is dysregulated, the overactivation of these responses can lead to the development of fibrosis (142). Notably, a previous study confirmed that the development of fibrosis is closely related to the production of Th2-type cytokines, mainly IL-4-mediated macrophage activation, fibroblast proliferation and differentiation, and ECM deposition, ultimately leading to PF formation (143).
IL-22. IL-22 is expressed by different types of lymphocytes, including CD4+ T cells, especially Th17, δγ T and NK cells (144). These cellular subpopulations express IL-22 with similar characteristics and unique mechanisms of expression (145). IL-22 differs from most ILs in that it does not directly regulate immune cell functions. Instead, IL-22 targets cells on extracorporeal barriers, such as the skin and tissues of the digestive and respiratory systems (146,147), as well as the pancreas, liver, kidneys and joints (148-151). IL-22 induces them to produce antimicrobial proteins and specific chemokines, whereas IL-17, TNF-α and IL-1β amplify this effect (152,153).
IL-22 exerts anti-inflammatory and antifibrotic effects (154). Cellular regeneration, tissue remodeling and homeostasis between commensal gut bacteria and the host immune system are the anti-inflammatory hallmarks of IL-22 (155,156). IL-22 is also important in intrinsic and adaptive immunity and is involved in various pathophysiological processes (157,158). For example, in mice infected with Klebsiella pneumoniae, IL-22 promotes epithelial repair and inhibits epithelial damage, thereby suppressing the inflammatory response (159). The antifibrotic effect of IL-22 is related to the protection of epithelial cells in in vivo and in vitro studies of PF, and it is an essential (155) immunomodulatory molecule in the lungs (159). It has been suggested that inhibition of the TGF-β pathway and collagen production by IL-22 reduces activation of Smad2/3 signaling in vitro (160). The mechanisms involved may not be clear, but it has been found that IL-22 mainly affects fibroblasts and epithelial cells (161), and it represents the main communication channel between specific tissue cell types and the immune system (162).
Notably, IL-22 was also reported to be a proinflammatory and profibrotic factor (163). IL-22 is capable of activating collagen production and deposition by stimulating fibroblast proliferation and secretion of profibrotic cytokines, which promote subepithelial fibrosis and lead to the remodeling of asthmatic airways (164).
3. Conclusion
ILs are a group of cytokines originating from diverse cell types and are known for their diverse effects. ILs can exert either antifibrotic or profibrotic effects and rarely exhibit dual actions by influencing the structure and functionality of various cell types involved in PF predominantly by targeting fibroblasts, macrophages and epithelial cells, which are closely associated with PF progression. The majority of the studies described in the present review still have some controversies. Therefore, a full understanding of ILs and their association with PF remains to be elucidated.
Acknowledgements
Not applicable.
Funding
Funding: This work was finally supported by Research Funds of Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine, Institute of Health and Medicine (grant no. 2023CXMMTCM007), Municipal Science and Technology Project of Wuhu Science and Technology Bureau (grant no. 2023yf090), Natural Science Foundation of the Higher Education Institutions of Anhui Province (grant no. 2023AH051751), Key Science and Technology Program of Wuhu City (grant no. 2022jc33) and Key Natural Science Research Project of Anhui Provincial Department of Education (grant no. KJ2021A0858).
Availability of data and materials
Not applicable.
Authors' contributions
SN and KZ contributed to the study conception and design. Material preparation, and data collection and analysis were performed by YH, XS, KZ and SN. The draft of the manuscript was written by YH, and all authors commented on previous versions of the manuscript. All authors read and approved the final version of the manuscript. Data authentication is not applicable.
Ethics approval and consent to participate
Not applicable.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
References
|
Ding DL, Shen XB, Yu LZ, Zheng YY, Liu Y, Wang W, Liu L, Zhao ZT, Nian SH and Liu LM: Timosaponin BII inhibits TGF-β mediated epithelial-mesenchymal transition through Smad-dependent pathway during pulmonary fibrosis. Phytother Res. 37:2787–2799. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Zhao T, Zhou Z, Wan H, Feng T, Hu X, Li X, Zhao S, Li H, Hou J, Li W, et al: Otilonium bromide ameliorates pulmonary fibrosis in mice through activating phosphatase PPM1A. Acta Pharmacol Sin: August 19, 2024 (Epub ahead of print). | |
|
Tu JY, Chen XY, Li CY, Liu CF, Huang YB, Wang X, Liang H and Yuan XL: Nintedanib mitigates radiation-induced pulmonary fibrosis by suppressing epithelial cell inflammatory response and inhibiting fibroblast-to-myofibroblast transition. Int J Biol Sci. 20:3353–3371. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Confalonieri P, Volpe MC, Jacob J, Maiocchi S, Salton F, Ruaro B, Confalonieri M and Braga L: Regeneration or repair? The role of alveolar epithelial cells in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Cells. 11(2095)2022.PubMed/NCBI View Article : Google Scholar | |
|
Kinoshita T and Goto T: Molecular mechanisms of pulmonary fibrogenesis and its progression to lung cancer: A review. Int J Mol Sci. 20(1461)2019.PubMed/NCBI View Article : Google Scholar | |
|
Pu Z, Sui B, Wang X, Wang W, Li L and Xie H: The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis. Phytomedicine. 114(154753)2023.PubMed/NCBI View Article : Google Scholar | |
|
Yang H, Hua C, Yang X, Fan X, Song H, Peng L and Ci X: Pterostilbene prevents LPS-induced early pulmonary fibrosis by suppressing oxidative stress, inflammation and apoptosis in vivo. Food Funct. 11:4471–4484. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Otoupalova E, Smith S, Cheng GJ and Thannickal VJ: Oxidative stress in pulmonary fibrosis. Compr Physiol. 10:509–547. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Valenca SS, Dong BE, Gordon EM, Sun RC and Waters CM: ASK1 regulates bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol. 66:484–496. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Tremayne P and John Clark S: Idiopathic pulmonary fibrosis: A more common condition than you may think. Br J Nurs. 30:359–366. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Hoyer N, Prior TS, Bendstrup E, Wilcke T and Shaker SB: Risk factors for diagnostic delay in idiopathic pulmonary fibrosis. Respir Res. 20(103)2019.PubMed/NCBI View Article : Google Scholar | |
|
Maher TM, Bendstrup E, Dron L, Langley J, Smith G, Khalid JM, Patel H and Kreuter M: Global incidence and prevalence of idiopathic pulmonary fibrosis. Respir Res. 22(197)2021.PubMed/NCBI View Article : Google Scholar | |
|
Glassberg MK: Overview of idiopathic pulmonary fibrosis, evidence-based guidelines, and recent developments in the treatment landscape. Am J Manag Care. 25 (11 Suppl):S195–S203. 2019.PubMed/NCBI | |
|
Agostini C and Gurrieri C: Chemokine/cytokine cocktail in idiopathic pulmonary fibrosis. Proc Am Thorac Soc. 3:357–363. 2006.PubMed/NCBI View Article : Google Scholar | |
|
Li H, Li Q and Hao Z, Zhang L, Zheng X, Zhu L, Huo Y, Tian H, He L and Hao Z: A recombinant IL-1β vaccine attenuates bleomycin-induced pulmonary fibrosis in mice. Vaccine. 42:3774–3788. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Park SJ, Ryu HW, Kim JH, Hahn HJ, Jang HJ, Ko SK, Oh SR and Lee HJ: Daphnetin alleviates bleomycin-induced pulmonary fibrosis through inhibition of epithelial-to-mesenchymal transition and IL-17A. Cells. 12(2795)2023.PubMed/NCBI View Article : Google Scholar | |
|
Xu X, Dai W and Li C: Interleukins in the treatment of melanoma. Chin Med J (Engl). 135:393–399. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Gritsenko A, Diaz-Pino R and López-Castejón G: NLRP3 inflammasome triggers interleukin-37 release from human monocytes. Eur J Immunol. 52:1141–1157. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Fukaura R and Akiyama M: Targeting IL-36 in inflammatory skin diseases. Biodrugs. 37:279–293. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Bequignon E, Mangin D, Bécaud J, Pasquier J, Angely C, Bottier M, Escudier E, Isabey D, Filoche M, Louis B, et al: Pathogenesis of chronic rhinosinusitis with nasal polyps: Role of IL-6 in airway epithelial cell dysfunction. J Transl Med. 18(136)2020.PubMed/NCBI View Article : Google Scholar | |
|
Mesas-Fernández A, Bodner E, Hilke FJ, Meier K, Ghoreschi K and Solimani F: Interleukin-21 in autoimmune and inflammatory skin diseases. Eur J Immunol. 53(e2250075)2023.PubMed/NCBI View Article : Google Scholar | |
|
Akdis M, Burgler S, Crameri R, Eiwegger T, Fujita H, Gomez E, Klunker S, Meyer N, O'Mahony L, Palomares O, et al: Interleukins, from 1 to 37, and interferon-γ: Receptors, functions, and roles in diseases. J Allergy Clin Immunol. 127:701–721.e1-e70. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Li Y, Yin H, Yuan H, Wang E, Wang C, Li H, Geng X, Zhang Y and Bai J: IL-10 deficiency aggravates cell senescence and accelerates BLM-induced pulmonary fibrosis in aged mice via PTEN/AKT/ERK pathway. BMC Pulm Med. 24(443)2024.PubMed/NCBI View Article : Google Scholar | |
|
Fattakhov N, Ngo A, Torices S, Joseph JA, Okoro A, Moore C, Naranjo O, Becker S and Toborek M: Cenicriviroc prevents dysregulation of astrocyte/endothelial cross talk induced by ischemia and HIV-1 via inhibiting the NLRP3 inflammasome and pyroptosis. Am J Physiol Cell Physiol. 326:C487–C504. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Chen P, Zhou J, Ruan AM, Ma YF and Wang QF: Paeoniflorin, the Main monomer component of paeonia lactiflora, exhibits anti-inflammatory properties in osteoarthritis synovial inflammation. Chin J Integr Med. 30:433–442. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Xiong Y, Cui X, Zhou Y, Chai G, Jiang X, Ge G, Wang Y, Sun H, Che H, Nie Y and Zhao P: Dehydrocostus lactone inhibits BLM-induced pulmonary fibrosis and inflammation in mice via the JNK and p38 MAPK-mediated NF-κB signaling pathways. Int Immunopharmacol. 98(107780)2021.PubMed/NCBI View Article : Google Scholar | |
|
Yan L, Hou C, Liu J, Wang Y, Zeng C, Yu J, Zhou T, Zhou Q, Duan S and Xiong W: Local administration of liposomal-based Plekhf1 gene therapy attenuates pulmonary fibrosis by modulating macrophage polarization. Sci China Life Sci. 66:2571–2586. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Zhang LM, Zhang Y, Fei C, Zhang J, Wang L, Yi ZW and Gao G: Neutralization of IL-18 by IL-18 binding protein ameliorates bleomycin-induced pulmonary fibrosis via inhibition of epithelial-mesenchymal transition. Biochem Biophys Res Commun. 508:660–666. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Xu X, Luo S, Li B, Dai H and Zhang J: IL-25 contributes to lung fibrosis by directly acting on alveolar epithelial cells and fibroblasts. Exp Biol Med (Maywood). 244:770–780. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Nie YJ, Wu SH, Xuan YH and Yan G: Role of IL-17 family cytokines in the progression of IPF from inflammation to fibrosis. Mil Med Res. 9(21)2022.PubMed/NCBI View Article : Google Scholar | |
|
Boersma B, Jiskoot W, Lowe P and Bourquin C: The interleukin-1 cytokine family members: Role in cancer pathogenesis and potential therapeutic applications in cancer immunotherapy. Cytokine Growth Factor Rev. 62:1–14. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Garlanda C and Mantovani A: Interleukin-1 in tumor progression, therapy, and prevention. Cancer Cell. 39:1023–1027. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Dinarello CA: Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood. 117:3720–3732. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Dinarello CA: Interleukin-1. Cytokine Growth Factor Rev. 8:253–265. 1997.PubMed/NCBI View Article : Google Scholar | |
|
Calverley PM, Sethi S, Dawson M, Ward CK, Finch DK, Penney M, Newbold P and van der Merwe R: A randomised, placebo-controlled trial of anti-interleukin-1 receptor 1 monoclonal antibody MEDI8968 in chronic obstructive pulmonary disease. Respir Res. 18(153)2017.PubMed/NCBI View Article : Google Scholar | |
|
Grönberg C, Rattik S, Tran-Manh C, Zhou X, Rius Rigau A, Li YN, Györfi AH, Dickel N, Kunz M, Kreuter A, et al: Combined inhibition of IL-1, IL-33 and IL-36 signalling by targeting IL1RAP ameliorates skin and lung fibrosis in preclinical models of systemic sclerosis. Ann Rheum Dis. 83:1156–1168. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Zhang YX, Zhang XT, Li HJ, Zhou TF, Zhou AC, Zhong ZL, Liu YH, Yuan LL, Zhu HY, Luan D and Tong JC: Antidepressant-like effects of helicid on a chronic unpredictable mild stress-induced depression rat model: Inhibiting the IKK/IκBα/NF-κB pathway through NCALD to reduce inflammation. Int Immunopharmacol. 93(107165)2021.PubMed/NCBI View Article : Google Scholar | |
|
Li W, Zhao X, Yu TT, Hao W and Wang GG: Knockout of PKC θ gene attenuates oleic acid-induced acute lung injury via reduction of inflammation and oxidative stress. Iran J Basic Med Sci. 24:986–991. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Witzenrath M and Kuebler WM: The lung-brain axis in ventilator-induced brain injury: Enter IL-6. Am J Respir Cell Mol Biol. 65:339–340. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Jones BE, Maerz MD and Buckner JH: IL-6: A cytokine at the crossroads of autoimmunity. Curr Opin Immunol. 55:9–14. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Le TTT, Karmouty-Quintana H, Melicoff E, Le TTT, Weng T, Chen NY, Pedroza M, Zhou Y, Davies J, Philip K, et al: Blockade of IL-6 trans signaling attenuates pulmonary fibrosis. J Immunol. 193:3755–3768. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Zhao FZ, Sang XQ, Zhu Y and Yang J: Effect and mechanism of IL-6 induced by M2 macrophages on the lung fibroblasts activation. Acta Pharmaceutica Sinica. 55:892–897. 2020. | |
|
Yang LB, Herrera J, Gilbertsen AJ, Xia H, Smith K, Benyumov A, Bitterman PB and Henke CA: IL-8 mediates idiopathic pulmonary fibrosis mesenchymal progenitor cell fibrogenicity. Am J Physiol Lung Cell Mol Physiol. 314:L127–L136. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Shochet GE, Brook E, Bardenstein-Wald B and Shitrit D: TGF-β pathway activation by idiopathic pulmonary fibrosis (IPF) fibroblast derived soluble factors is mediated by IL-6 trans-signaling. Respir Res. 12(56)2020.PubMed/NCBI View Article : Google Scholar | |
|
Liu Y, Lu F, Kang L, Wang Z and Wang Y: Pirfenidone attenuates bleomycin-induced pulmonary fibrosis in mice by regulating Nrf2/Bach1 equilibrium. BMC Pulm Med. 17(63)2017.PubMed/NCBI View Article : Google Scholar | |
|
Cebi M and Yilmaz Y: Immune system dysregulation in the pathogenesis of non-alcoholic steatohepatitis: Unveiling the critical role of T and B lymphocytes. Front Immunol. 15(1445634)2024.PubMed/NCBI View Article : Google Scholar | |
|
Read J, Reid AT, Thomson C, Plit M, Mejia R, Knight DA, Lize M, Kasmi KE, Grainge CL, Stahl H and Schuliga M: Alveolar epithelial cells of lung fibrosis patients are susceptible to severe virus-induced injury. Clin Sci (Lond). 138:537–554. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Jøntvedt Jørgensen M, Holter JC, Christensen EE, Schjalm C, Tonby K, Pischke SE, Jenum S, Skeie LG, Nur S, Lind A, et al: Increased interleukin-6 and macrophage chemoattractant protein-1 are associated with respiratory failure in COVID-19. Sci Rep. 10(21697)2020.PubMed/NCBI View Article : Google Scholar | |
|
Khanna D, Lin CJF, Furst DE, Goldin J, Kim G, Kuwana M, Allanore Y, Matucci-Cerinic M, Distler O, Shima Y, et al: Tocilizumab in systemic sclerosis: A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 8:963–974. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Sagaram M, Frimodig J, Jayanty D, Hu H, Royer AJ, Bruner R, Kong M, Schwandt ML and Vatsalya V: One-month assessment of Th-cell axis related inflammatory cytokines, IL-17 and IL-22 and their role in alcohol-associated liver disease. Front Immunol. 14(1202267)2023.PubMed/NCBI View Article : Google Scholar | |
|
Kosmopoulos M, Christofides A, Drekolias D, Zavras PD, Gargalionis AN and Piperi C: Critical role of IL-8 targeting in gliomas. Curr Med Chem. 25:1954–1967. 2018.PubMed/NCBI View Article : Google Scholar | |
|
W.Y. B: Changes of IL-2R, IL-6, IL-8, and TNF-α in diffuse large B-cell lymphoma and their significance. J Clin Hematol. 36:33–38. 2023. | |
|
Papiris SA, Tomos IP, Karakatsani A, Spathis A, Korbila I, Analitis A, Kolilekas L, Kagouridis K, Loukides S, Karakitsos P and Manali ED: High levels of IL-6 and IL-8 characterize early-on idiopathic pulmonary fibrosis acute exacerbations. Cytokine. 102:168–172. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Yang L, Xia H, Gilbertsen A, Smith K, Racila E, Bitterman PB and Henke CA: IL-8 concurrently promotes idiopathic pulmonary fibrosis mesenchymal progenitor cell senescence and PD-L1 expression enabling escape from immune cell surveillance. Am J Physiol Lung Cell Mol Physiol. 324:L849–L862. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Li Y, Su G, Zhong Y, Xiong Z, Huang T, Quan J, Huang J, Wen X, Luo C, Zheng W, et al: HB-EGF-induced IL-8 secretion from airway epithelium leads to lung fibroblast proliferation and migration. BMC Pulm Med. 21(347)2021.PubMed/NCBI View Article : Google Scholar | |
|
Kato A: Immunopathology of chronic rhinosinusitis. Allergol Int. 64:121–130. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Moonwiriyakit A, Yimnual C, Noitem R, Dinsuwannakol S, Sontikun J, Kaewin S, Worakajit N, Soontornniyomkij V and Muanprasat C: GPR120/FFAR4 stimulation attenuates airway remodeling and suppresses IL-4- and IL-13-induced airway epithelial injury via inhibition of STAT6 and Akt. Biomed Pharmacother. 168(115774)2023.PubMed/NCBI View Article : Google Scholar | |
|
Iwaszko M, Biały S and Bogunia-Kubik K: Significance of interleukin (IL)-4 and IL-13 in inflammatory arthritis. Cells. 10(3000)2021.PubMed/NCBI View Article : Google Scholar | |
|
Husna SMN, Shukri NM, Ashari NSM and Wong KK: IL-4/IL-13 axis as therapeutic targets in allergic rhinitis and asthma. PeerJ. 10(e13444)2022.PubMed/NCBI View Article : Google Scholar | |
|
Bonser LR, Eckalbar WL, Rodriguez L, Shen J, Koh KD, Ghias K, Zlock LT, Christenson S, Woodruff PG, Finkbeiner WE and Erle DJ: The type 2 asthma mediator IL-13 inhibits severe acute respiratory syndrome coronavirus 2 infection of bronchial epithelium. Am J Respir Cell Mol Biol. 66:391–401. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Le Floc'h A, Allinne J, Nagashima K, Scott G, Birchard D, Asrat S, Bai Y, Lim WK, Martin J, Huang T, et al: Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Rα antibody, is required to broadly inhibit type 2 inflammation. Allergy. 75:1188–1204. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Passalacqua G, Mincarini M, Colombo D, Troisi G, Ferrari M, Bagnasco D, Balbi F, Riccio A and Canonica GW: IL-13 and idiopathic pulmonary fibrosis: Possible links and new therapeutic strategies. Pulm Pharmacol Ther. 45:95–100. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Bhatt SP, Rabe KF, Hanania NA, Vogelmeier CF, Cole J, Bafadhel M, Christenson SA, Papi A, Singh D, Laws E, et al: Dupilumab for COPD with type 2 inflammation indicated by eosinophil counts. N Engl J Med. 389:205–214. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Maher TM, Costabel U, Glassberg MK, Kondoh Y, Ogura T, Scholand MB, Kardatzke D, Howard M, Olsson J, Neighbors M, et al: Phase 2 trial to assess lebrikizumab in patients with idiopathic pulmonary fibrosis. Eur Respir J. 57(1902442)2021.PubMed/NCBI View Article : Google Scholar | |
|
Shaikh SB, Prabhu A and Bhandary YP: Interleukin-17A: A potential therapeutic target in chronic lung diseases. Endocr Metab Immune Disord Drug Targets. 19:921–928. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Berry SPDG, Dossou C, Kashif A, Sharifinejad N, Azizi G, Hamedifar H, Sabzvari A and Zian Z: The role of IL-17 and anti-IL-17 agents in the immunopathogenesis and management of autoimmune and inflammatory diseases. Int Immunopharmacol. 102(108402)2022.PubMed/NCBI View Article : Google Scholar | |
|
Yang Z, Zhang J, Zhu Y, Zhang C, Li G, Liu S, Du J, Han Y and You B: IL-17A induces valvular endothelial inflammation and aggravates calcific aortic valve disease. Biochem Biophys Res Commun. 672:145–153. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Luo J, An X, Yao Y, Erb C, Ferguson A, Kolls JK, Fan S and Chen K: Epigenetic regulation of IL-17-induced chemokines in lung epithelial cells. Mediators Inflamm. 2019(9050965)2019.PubMed/NCBI View Article : Google Scholar | |
|
Lei L, Zhao C, Qin F, He ZY, Wang X and Zhong XN: Th17 cells and IL-17 promote the skin and lung inflammation and fibrosis process in a bleomycin-induced murine model of systemic sclerosis. Clin Exp Rheumatol. 34 (Suppl 100):S14–S22. 2016.PubMed/NCBI | |
|
Gouda MM and Bhandary YP: Acute lung injury: IL-17A-mediated inflammatory pathway and its regulation by curcumin. Inflammation. 42:1160–1169. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Roos AB, Mori M, Gura HK, Lorentz A, Bjermer L, Hoffmann HJ, Erjefält JS and Stampfli MR: Increased IL-17RA and IL-17RC in end-stage COPD and the contribution to mast cell secretion of FGF-2 and VEGF. Respir Res. 18(48)2017.PubMed/NCBI View Article : Google Scholar | |
|
Miossec P and Kolls JK: Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 11:763–776. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Rex DAB, Dagamajalu S, Gouda MM, Suchitha GP, Chanderasekaran J, Raju R, Prasad TSK and Bhandary YP: A comprehensive network map of IL-17A signaling pathway. J Cell Commun Signal. 17:209–215. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Schmidt T, Luebbe J, Kilian C, Riedel JH, Hiekmann S, Asada N, Ginsberg P, Robben L, Song N, Kaffke A, et al: IL-17 receptor C signaling controls CD4+ TH17 immune responses and tissue injury in immune-mediated kidney diseases. J Am Soc Nephrol. 32:3081–3098. 2021.PubMed/NCBI View Article : Google Scholar | |
|
He F, Yu X, Zhang J, Cui J, Tang L, Zou S, Pu J and Ran P: Biomass-related PM2.5 induced inflammatory microenvironment via IL-17F/IL-17RC axis. Environ Pollut. 342(123048)2024.PubMed/NCBI View Article : Google Scholar | |
|
Ni Q, Li G, Chen Y, Bao C, Wang T, Li Y, Ruan X, Wang H and Sun W: LECs regulate neutrophil clearance through IL-17RC/CMTM4/NF-κB axis at sites of inflammation or infection. Mucosal Immunol. 17:723–738. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Park SJ, Hahn HJ, Oh SR and Lee HJ: Theophylline attenuates BLM-induced pulmonary fibrosis by inhibiting Th17 differentiation. Int J Mol Sci. 24(1019)2023.PubMed/NCBI View Article : Google Scholar | |
|
Maxwell JR, Yadav R, Rossi RJ, Ruby CE, Weinberg AD, Aguila HL and Vella AT: IL-18 bridges innate and adaptive immunity through IFN-gamma and the CD134 pathway. J Immunol. 177:234–245. 2006.PubMed/NCBI View Article : Google Scholar | |
|
Shao XF, Li B, Shen J, Wang QF, Chen SS, Jiang XC and Qiang D: Ghrelin alleviates traumatic brain injury-induced acute lung injury through pyroptosis/NF-κB pathway. Int Immunopharmacol. 79(106175)2020.PubMed/NCBI View Article : Google Scholar | |
|
Kobori T, Hamasaki S, Kitaura A, Yamazaki Y, Nishinaka T, Niwa A, Nakao S, Wake H, Mori S, Yoshino T, et al: Interleukin-18 amplifies macrophage polarization and morphological alteration, leading to excessive angiogenesis. Front Immunol. 9(334)2018.PubMed/NCBI View Article : Google Scholar | |
|
Cai G, Lu Y, Zhong W, Wang T, Li Y, Ruan X, Chen H, Sun L, Guan Z, Li G, et al: Piezo1-mediated M2 macrophage mechanotransduction enhances bone formation through secretion and activation of transforming growth factor-β1. Cell Prolif. 56(e13440)2023.PubMed/NCBI View Article : Google Scholar | |
|
Zhang C, Zhu X, Hua Y, Zhao Q, Wang K, Zhen L, Wang G, Lü J, Luo A, Cho WC, et al: YY1 mediates TGF-β1-induced EMT and pro-fibrogenesis in alveolar epithelial cells. Respir Res. 20(249)2019.PubMed/NCBI View Article : Google Scholar | |
|
Ibi M, Horie S, Kyakumoto S, Chosa N, Yoshida M, Kamo M, Ohtsuka M and Ishisaki A: Cell-cell interactions between monocytes/macrophages and synoviocyte-like cells promote inflammatory cell infiltration mediated by augmentation of MCP-1 production in temporomandibular joint. Biosci Rep. 38(BSR20171217)2018.PubMed/NCBI View Article : Google Scholar | |
|
Wu L, Pu L and Zhuang Z: miR-155-5p/FOXO3a promotes pulmonary fibrosis in rats by mediating NLRP3 inflammasome activation. Immunopharmacol Immunotoxicol. 45:257–267. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Schinocca C, Rizzo C, Fasano S, Grasso G, La Barbera L, Ciccia F and Guggino G: Role of the IL-23/IL-17 pathway in rheumatic diseases: An overview. Front Immunol. 12(637829)2021.PubMed/NCBI View Article : Google Scholar | |
|
Zhang Q, Tong L, Wang B, Wang T and Ma H: Diagnostic value of serum levels of IL-22, IL-23, and il-17 for idiopathic pulmonary fibrosis associated with lung cancer. Ther Clin Risk Manag. 18:429–437. 2022.PubMed/NCBI View Article : Google Scholar | |
|
Bhattacharya G, Sengupta S, Jha R, Shaw SK, Jogdand GM, Barink PK, Padhan P, Parida JR and Devadas S: IL-21/23 axis modulates inflammatory cytokines and RANKL expression in RA CD4+ T cells via p-Akt1 signaling. Front Immunol. 14(1235514)2023.PubMed/NCBI View Article : Google Scholar | |
|
Loo WJ, Turchin I, Prajapati VH, Gooderham MJ, Grewal P, Hong CH, Sauder M, Vender RB, Maari C and Papp KA: Clinical implications of targeting the JAK-STAT pathway in psoriatic disease: Emphasis on the TYK2 pathway. J Cutan Med Surg. 27 (1 Suppl):3S–24S. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Vuyyuru SK, Shackelton LM, Hanzel J, Ma C, Jairath V and Feagan BG: Targeting IL-23 for IBD: Rationale and progress to date. Drugs. 83:873–891. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Ogishi M, Arias AA, Yang R, Han JE, Zhang P, Rinchai D, Halpern J, Mulwa J, Keating N, Chrabieh M, et al: Impaired IL-23-dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency. J Exp Med. 219(e20220094)2022.PubMed/NCBI View Article : Google Scholar | |
|
Senoo S, Taniguchi A, Itano J, Oda N, Morichika D, Fujii U, Guo L, Sunami R, Kanehiro A, Tokioka F, et al: Essential role of IL-23 in the development of acute exacerbation of pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 321:L925–L940. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Sanada S, Hakuno D, Higgins LJ, Schreiter ER, McKenzie ANJ and Lee RT: IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest. 117:1538–1549. 2007.PubMed/NCBI View Article : Google Scholar | |
|
Piyadasa H, Lloyd D, Lee AHY, Altieri A, Hemshekhar M, Osawa N, Basu S, Blimkie T, Falsafi R, Halayko AJ, et al: Characterization of immune responses and the lung transcriptome in a murine model of IL-33 challenge. Biochim Biophys Acta Mol Basis Dis. 1866(165950)2020.PubMed/NCBI View Article : Google Scholar | |
|
Drake LY and Kita H: IL-33: Biological properties, functions, and roles in airway disease. Immunol Rev. 278:173–184. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Chen YL, Gutowska-Owsiak D, Hardman CS, Westmoreland M, MacKenzie T, Cifuentes L, Waithe D, Lloyd-Lavery A, Marquette A, Londei M and Ogg C: Proof-of-concept clinical trial of etokimab shows a key role for IL-33 in atopic dermatitis pathogenesis. Sci Transl Med. 11(eaax2945)2019.PubMed/NCBI View Article : Google Scholar | |
|
Kosloski MP, Kalliolias GD, Xu CR, Harel S, Lai CH, Zheng W, Davis JD and Kamal MA: Pharmacokinetics and pharmacodynamics of itepekimab in healthy adults and patients with asthma: Phase I first-in-human and first-in-patient trials. Clin Transl Sci. 15:384–395. 2022.PubMed/NCBI View Article : Google Scholar | |
|
She YX, Yu QY and Tang XX: Role of interleukins in the pathogenesis of pulmonary fibrosis. Cell Death Discov. 7(52)2021.PubMed/NCBI View Article : Google Scholar | |
|
Jayalatha AS, Hesse L, Ketelaar ME, Koppelman GH and Nawijn MC: The central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to intervention. Pharmacol Ther. 225(107847)2021.PubMed/NCBI View Article : Google Scholar | |
|
Nechama M, Kwon J, Wei S, Kyi AT, Welner RS, Ben-Dov IZ, Arredouani MS, Asara JM, Chen CH, Tsai CY, et al: The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity in IL-33-induced allergic airway inflammation. Nat Commun. 9(1603)2018.PubMed/NCBI View Article : Google Scholar | |
|
Reid F, Singh D, Albayaty M, Moate R, Jimenez E, Sadiq MW, Howe D, Gavala M, Killick H, Williams A, et al: A randomized phase I study of the anti-interleukin-33 antibody Tozorakimab in healthy adults and patients with chronic obstructive pulmonary disease. Clin Pharmacol Ther. 115:565–575. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Catalan-Dibene J, McIntyre LL and Zlotnik A: Interleukin 30 to interleukin 40. J Interferon Cytokine Res. 38:423–439. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Borthwick LA: The IL-1 cytokine family and its role in inflammation and fibrosis in the lung. Semin Immunopathol. 38:517–534. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Andoh A and Nishida A: Pro- and anti-inflammatory roles of interleukin (IL)-33, IL-36, and IL-38 in inflammatory bowel disease. J Gastroenterol. 58:69–78. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Aoyagi T, Newstead MW, Zeng XY, Kunkel SL, Kaku M and Standiford TJ: IL-36 receptor deletion attenuates lung injury and decreases mortality in murine influenza pneumonia. Mucosal Immunol. 10:1043–1055. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Vigne S, Palmer G, Lamacchia C, Martin P, Talabot-Ayer D, Rodriguez E, Ronchi F, Sallusto F, Dinh H, Sims JE and Gabay C: IL-36R ligands are potent regulators of dendritic and T cells. Blood. 118:5813–5823. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Cao J, Liu JH, Wise SG, Fan J, Bao S and Zheng GS: The role of IL-36 and 37 in hepatocellular carcinoma. Front Immunol. 15(1281121)2024.PubMed/NCBI View Article : Google Scholar | |
|
Elias M, Zhao S, Le HT, Wang J, Neurath MF, Neufert C, Fiocchi C and Rieder F: IL-36 in chronic inflammation and fibrosis-bridging the gap? J Clin Invest. 131(144336)2021.PubMed/NCBI View Article : Google Scholar | |
|
Montero-Blay A, Blanco JD, Rodriguez-Arce I, Lastrucci C, Piñero-Lambea C, Lluch-Senar M and Serrano L: Bacterial expression of a designed single-chain IL-10 prevents severe lung inflammation. Mol Syst Biol. 19(e11037)2023.PubMed/NCBI View Article : Google Scholar | |
|
Huaux F: Interpreting immunoregulation in lung fibrosis: A new branch of the immune model. Front Immunol. 12(690375)2021.PubMed/NCBI View Article : Google Scholar | |
|
Gabryšová L, Howes A, Saraiva M and O'Garra A: The regulation of IL-10 expression. Curr Top Microbiol Immunol. 380:157–190. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Saraiva M, Vieira P and O'garra A: Biology and therapeutic potential of interleukin-10. J Exp Med. 217(e20190418)2020.PubMed/NCBI View Article : Google Scholar | |
|
Chlastáková A, Kaščáková B, Kotál J, Langhansová H, Kotsyfakis M, Kutá Smatanová I, Tirloni L and Chmelař J: Iripin-1, a new anti-inflammatory tick serpin, inhibits leukocyte recruitment in vivo while altering the levels of chemokines and adhesion molecules. Front Immunol. 14(1116324)2023.PubMed/NCBI View Article : Google Scholar | |
|
Neumann C, Scheffold A and Rutz S: Functions and regulation of T cell-derived interleukin-10. Semin Immunol. 44(101344)2019.PubMed/NCBI View Article : Google Scholar | |
|
Zhang N, Li P, Lin H, Shuo T, Ping F, Su L and Chen G: IL-10 ameliorates PM2.5-induced lung injury by activating the AMPK/SIRT1/PGC-1α pathway. Environ Toxicol Pharmacol. 86(103659)2021.PubMed/NCBI View Article : Google Scholar | |
|
Jia Q, Wen J, Yang Q, Liu S, Zhang J, Wang T and Cheng Y: Lonicera japonica Thunb extract ameliorates lipopolysaccharide-induced acute lung injury associated with luteolin-mediated suppression of NF-κB signaling pathway. J Inflamm (Lond). 20(44)2023.PubMed/NCBI View Article : Google Scholar | |
|
Boonyatecha N, Sangphech N, Wongchana W, Kueanjinda P and Palaga T: Involvement of Notch signaling pathway in regulating IL-12 expression via c-Rel in activated macrophages. Mol Immunol. 51:255–262. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Utsunomiya T, Mimura-Kimura Y, Yamamoto T, Aoe K, Oishi K, Kamei H, Matsunaga K, Yano M and Mimura Y: Cytokine adsorption to polymyxin B-immobilized fiber: An in vitro study. Blood Purif. 50:230–237. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Zhou L, Tian H, Wang Q, Xiong W, Zhou X and Yan J: Effect of Qingfei Huaxian Decoction combined with prednisone acetate on serum inflammatory factors and pulmonary function of patients with idiopathic pulmonary fibrosis. Am J Transl Res. 14:5905–5914. 2022.PubMed/NCBI | |
|
Kotani T, Masutani R, Suzuka T, Oda K, Makino S and Ii M: Anti-inflammatory and anti-fibrotic effects of intravenous adipose-derived stem cell transplantation in a mouse model of bleomycin-induced interstitial pneumonia. Sci Rep. 7(14608)2017.PubMed/NCBI View Article : Google Scholar | |
|
Bao L, Hao CF, Liu SN, Zhang L, Wang J, Wang D, Li YP and Yao W: Dendritic cells trigger imbalance of Th1/Th2 cells in silica dust exposure rat model via MHC-II, CD80, CD86 and IL-12. RSC Adv. 8:26108–26115. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Keane MP, Belperio JA, Burdick MD and Strieter RM: IL-12 attenuates bleomycin-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 281:L92–L97. 2001.PubMed/NCBI View Article : Google Scholar | |
|
Nie Y, Yang B, Hu J, Zhang L and Ma Z: Bruceine D ameliorates the balance of Th1/Th2 in a mouse model of ovalbumin-induced allergic asthma via inhibiting the NOTCH pathway. Allergol Immunopathol (Madr). 49:73–79. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Kikuchi N, Ishii Y, Morishima Y, Yageta Y, Haraguchi N, Itoh K, Yamamoto M and Hizawa N: Nrf2 protects against pulmonary fibrosis by regulating the lung oxidant level and Th1/Th2 balance. Respir Res. 11(31)2010.PubMed/NCBI View Article : Google Scholar | |
|
Huaux F, Lardot C, Arras M, Delos M, Many MC, Coutelier JP, Buchet JP, Renauld JC and Lison D: Lung fibrosis induced by silica particles in NMRI mice is associated with an upregulation of the p40 subunit of interleukin-12 and Th-2 manifestations. Am J Respir Cell Mol Biol. 20:561–672. 1999.PubMed/NCBI View Article : Google Scholar | |
|
Wang XY, Liu DY, Zhang XH, Yang LM, Xia ZY and Zhang QF: Exosomes from adipose-derived mesenchymal stem cells alleviate sepsis-induced lung injury in mice by inhibiting the secretion of IL-27 in macrophages. Cell Death Discov. 8(18)2022.PubMed/NCBI View Article : Google Scholar | |
|
Chen Y, Zhu M, Hu J, He S, Li S, Liu B and Yang J: IL-27 alleviates airway inflammation and airway hyperresponsiveness in asthmatic mice by targeting the CD39/ATP axis of dendritic cells. Inflammation. 47:807–821. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Dong Z, Zhao X, Tai W, Lei W, Wang Y, Li Z and Zhang T: IL-27 attenuates the TGF-β1-induced proliferation, differentiation and collagen synthesis in lung fibroblasts. Life Sci. 146:24–33. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Dong Z, Tai W, Lei W, Wang Y, Li Z and Zhang T: IL-27 inhibits the TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells. BMC Cell Biol. 17(7)2016.PubMed/NCBI View Article : Google Scholar | |
|
Ting L, Feng Y, Zhou Y, Tong Z and Dong Z: IL-27 induces autophagy through regulation of the DNMT1/lncRNA MEG3/ERK/p38 axis to reduce pulmonary fibrosis. Respir Res. 24(67)2023.PubMed/NCBI View Article : Google Scholar | |
|
Riehl DR, Sharma A, Roewe J, Murke F, Ruppert C, Eming SA, Bopp T, Kleinert H, Radsak MP, Colucci G, et al: Externalized histones fuel pulmonary fibrosis via a platelet-macrophage circuit of TGFβ1 and IL-27. Proc Natl Acad Sci USA. 120(e2215421120)2023.PubMed/NCBI View Article : Google Scholar | |
|
Dinarello CA and Bufler P: Interleukin-37. Semin Immunol. 25:466–468. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Kim SK, Choe JY, Kim JW, Park KY and Kim B: Anti-inflammatory effect of atorvastatin and rosuvastatin on monosodium urate-induced inflammation through IL-37/Smad3-complex activation in an in vitro study using THP-1 macrophages. Pharmaceuticals (Basel). 17(883)2024.PubMed/NCBI View Article : Google Scholar | |
|
Luo C, Shu Y, Luo J, Liu D, Huang DS, Han Y, Chen C, Li YC, Zou JM, Qin J, et al: Intracellular IL-37b interacts with Smad3 to suppress multiple signaling pathways and the metastatic phenotype of tumor cells. Oncogene. 36:2889–2899. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Conti P, Caraffa A, Gallenga CE, Ross R, Kritas SK, Frydas I, Younes A, Di Emidio P, Ronconi G and Pandolfi F: Powerful anti-inflammatory action of luteolin: Potential increase with IL-38. Biofactors. 47:165–169. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Diaz-Barreiro A, Huard A and Palmer G: Multifaceted roles of IL-38 in inflammation and cancer. Cytokine. 151(155808)2022.PubMed/NCBI View Article : Google Scholar | |
|
Chen W, Xi S, Ke Y and Lei Y: The emerging role of IL-38 in diseases: A comprehensive review. Immun Inflamm Dis. 11(e991)2023.PubMed/NCBI View Article : Google Scholar | |
|
van de Veerdonk FL, de Graaf DM, Joosten LA and Dinarello CA: Biology of IL-38 and its role in disease. Immunol Rev. 281:191–196. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Xu Z, Yuan X, Gao Q, Li Y and Li M: Interleukin-38 overexpression prevents bleomycin-induced mouse pulmonary fibrosis. Naunyn Schmiedebergs Arch Pharmacol. 394:391–399. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Kelly-Welch A, Hanson EM and Keegan AD: Interleukin-4 (IL-4) pathway. Sci STKE. 2005(cm9)2005.PubMed/NCBI View Article : Google Scholar | |
|
Rao LZ, Wang Y, Zhang L, Wu G, Zhang L, Wang FX, Chen LM, Sun F, Jia S, Zhang S, et al: IL-24 deficiency protects mice against bleomycin-induced pulmonary fibrosis by repressing IL-4-induced M2 program in macrophages. Cell Death Differ. 28:1270–1283. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Sterclova M, Kishore A, Sikorova K, Skibova J, Petrek M and Vasakova M: Effect of genotype on the disease course in idiopathic pulmonary fibrosis despite antifibrotic treatment. Biomed Rep. 15(87)2021.PubMed/NCBI View Article : Google Scholar | |
|
Singh B, Kasam RK, Sontake V, Wynn TA and Madala SK: Repetitive intradermal bleomycin injections evoke T-helper cell 2 cytokine-driven pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 313:L796–L806. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Mattoo H, Bangari DS, Cummings S, Humulock Z, Habiel D, Xu EY, Pate N, Resnick R, Savova V, Qian G, et al: Molecular features and stages of pulmonary fibrosis driven by type 2 inflammation. Am J Respir Cell Mol Biol. 69:404–421. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Khansalar S, Faghih Z, Barani S, Kalani M, Ataollahi MR, Mohammadi Z, Namdari S and Kalantar K: IFN-γ, IL-17, IL-22+ CD4+ subset in patients with hepatitis C virus and correlation with clinical factor. Am J Clin Exp Immunol. 13:43–52. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Liang M, Wang J, Chu H, Zhu X, He H, Liu Q, Qiu J, Zhou X, Guan M, Xue Y, et al: Interleukin-22 inhibits bleomycin-induced pulmonary fibrosis. Mediators Inflamm. 2013(209179)2013.PubMed/NCBI View Article : Google Scholar | |
|
Bao A, Ma E, Cornman H, Kambala A, Manjunath J, Kollhoff AL, Imo BU, Kwatra MM and Kwatra SG: Dupilumab therapy modulates circulating inflammatory mediators in patients with prurigo nodularis. JID Innov. 4(100281)2024.PubMed/NCBI View Article : Google Scholar | |
|
Liu J, Huang Y, Liu N, Qiu H, Zhang X, Liu X, He M, Chen M and Huang S: The imbalance of pulmonary Th17/Treg cells in BALB/c suckling mice infected with respiratory syncytial virus-mediated intestinal immune damage and gut microbiota changes. Microbiol Spectr. 12(e0328323)2024.PubMed/NCBI View Article : Google Scholar | |
|
Li C, Liu M, Deng L, Luo D, Ma R and Lu Q: Oxyberberine ameliorates TNBS-induced colitis in rats through suppressing inflammation and oxidative stress via Keap1/Nrf2/NF-κB signaling pathways. Phytomedicine. 116(154899)2023.PubMed/NCBI View Article : Google Scholar | |
|
Zhang J, Wang W, Liang S, Zhou X, Rekha RS, Gudmundsson GH, Bergman P, Ai Q, Mai K and Wan M: Butyrate induces STAT3/HIF-1α/IL-22 signaling via GPCR and HDAC3 inhibition to activate autophagy in head kidney macrophages from turbot (Scophthalmus maximus L.). Fish Shellfish Immunol. 143(109214)2023.PubMed/NCBI View Article : Google Scholar | |
|
Sajiir H, Keshvari S, Wong KY, Borg DJ, Steyn FJ, Fercher C, Taylor K, Taylor B, Barnard RT, Müller A, et al: Liver and pancreatic-targeted interleukin-22 as a therapeutic for metabolic dysfunction-associated steatohepatitis. Nat Commun. 15(4528)2024.PubMed/NCBI View Article : Google Scholar | |
|
Kamata K, Hara A, Minaga K, Yoshikawa T, Kurimoto M, Sekai I, Okai N, Omaru N, Masuta Y, Otsuka Y, et al: Activation of the aryl hydrocarbon receptor inhibits the development of experimental autoimmune pancreatitis through IL-22-mediated signaling pathways. Clin Exp Immunol. 212:171–183. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Zhang Z, Chakawa MB, Galeas-Pena M, Frydman JA, Allen MJ, Jones M and Pociask D: IL-22 binding protein controls IL-22-driven bleomycin-induced lung injury. Am J Pathol. 194:338–352. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Goulart A, Boko MMM, Martins NS, Gembre AF, de Oliveira RS, Palma-Albornoz SP, Bertolini T, Ribolla PEM, Ramalho LNZ, Fraga-Silva TFC and Bonato VLD: IL-22 is deleterious along with IL-17 in allergic asthma but is not detrimental in the comorbidity asthma and acute pneumonia. Int J Mol Sci. 24(10418)2023.PubMed/NCBI View Article : Google Scholar | |
|
He G, Lang Y, Zhao S, Wang X and Ouyang Y: Advances in the role of interleukin-22 in airway remodeling in asthma. J Pract Med. 38:2491–2494. 2022. | |
|
Nikoopour E, Bellemore SM and Singh B: IL-22, cell regeneration and autoimmunity. Cytokine. 74:35–42. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Zindl CL, Wilson CG, Chadha AS, Duck LW, Cai B, Harbour SN, Nagaoka-Kamata Y, Hatton RD, Gao M, Figge DA and Weaver CT: Distal colonocytes targeted by C. rodentium recruit T-cell help for barrier defence. Nature. 629:669–678. 2024.PubMed/NCBI View Article : Google Scholar | |
|
Whittington HA, Armstrong L, Uppington KM and Millar AB: Interleukin-22: A potential immunomodulatory molecule in the lung. Am J Respir Cell Mol Biol. 31:220–226. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Zhang C, Tang S, Zong X, Duan L and Wang YF: Anti- IL-22 neutralizing antibodies decrease inflammation lesions and reduce mortality in enterovirus 71-infected mice. Cell Mol Biol (Noisy-le-grand). 69:254–258. 2023.PubMed/NCBI View Article : Google Scholar | |
|
Qu Z, Dou W, Zhang K, Duan L, Zhou D and Yin S: IL-22 inhibits bleomycin-induced pulmonary fibrosis in association with inhibition of IL-17A in mice. Arthritis Res Ther. 24(280)2022.PubMed/NCBI View Article : Google Scholar | |
|
Gu P, Wang D, Zhang J, Wang X, Chen Z, Gu L, Liu M, Meng F, Yang J, Cai H, et al: Protective function of interleukin-22 in pulmonary fibrosis. Clin Transl Med. 11(e509)2021.PubMed/NCBI View Article : Google Scholar | |
|
Fang S, Ju DW, Lin Y and Chen W: The role of interleukin-22 in lung health and its therapeutic potential for COVID-19. Front Immunol. 13(951107)2022.PubMed/NCBI View Article : Google Scholar | |
|
Fang Q, Xie J, Zong J, Zhou Y, Zhou Q, Yin S, Cao L, Yin H and Zhou D: Expression and diagnostic value of interleukin-22 in rheumatoid arthritis-associated interstitial lung disease. Int Immunopharmacol. 134(112173)2024.PubMed/NCBI View Article : Google Scholar | |
|
Wu Y, Min J, Ge C, Shu JP, Tian D, Yuan Y and Zhou D: Interleukin 22 in liver injury, inflammation and cancer. Int J Biol Sci. 16(2405)2020.PubMed/NCBI View Article : Google Scholar | |
|
Beppu AK, Zhao J, Yao C, Carraro G, Israely E, Coelho AL, Drake K, Hogaboam CM, Parks WC, Kolls JK and Stripp BR: Epithelial plasticity and innate immune activation promote lung tissue remodeling following respiratory viral infection. Nat Commun. 14(5814)2023.PubMed/NCBI View Article : Google Scholar |
