Irisin attenuates acute lung injury by suppressing the pyroptosis of alveolar macrophages

Han,Zhuoxiao; Ma,Jiao; Han,Ying; Yuan,Guanli; Jiao,Rui; Meng,Aihong

doi:10.3892/ijmm.2023.5235

Irisin attenuates acute lung injury by suppressing the pyroptosis of alveolar macrophages

Authors:
- Zhuoxiao Han
- Jiao Ma
- Ying Han
- Guanli Yuan
- Rui Jiao
- Aihong Meng
View Affiliations

Affiliations: Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Neurosurgery, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei 066000, P.R. China, Department of Respiratory and Critical Care Medicine, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei 066000, P.R. China
Published online on: March 7, 2023 https://doi.org/10.3892/ijmm.2023.5235
Article Number: 32
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Irisin is a hormone‑like myokine that regulates cell signaling pathways and exerts anti‑inflammatory effects. However, the specific molecular mechanisms involved in this process are currently unknown. The present study explored the role and mechanisms underlying the functions of irisin in alleviating acute lung injury (ALI). The present study used MH‑S, an established murine alveolar macrophage‑derived cell line, and a mouse model of lipopolysaccharide (LPS)‑induced‑ALI to examine the efficacy of irisin against ALI in vitro and in vivo, respectively. Fibronectin type III repeat‑containing protein/irisin was expressed in the inflamed lung tissue, but not in normal lung tissue. Exogenous irisin reduced alveolar inflammatory cell infiltration and pro‑inflammatory factor secretion in mice following LPS stimulation. It also inhibited the polarization of M1‑type macrophages and promoted the repolarization of M2‑type macrophages, thus reducing the LPS‑induced production and secretion of interleukin (IL)‑1β, IL‑18 and tumor necrosis factor‑α. In addition, irisin reduced the release of the molecular chaperone heat shock protein 90 (HSP90), inhibited the formation of nucleotide‑binding and oligomerization domain‑like receptor protein 3 (NLRP3) inflammasome complexes, and decreased the expression of caspase‑1 and the cleavage of gasdermin D (GSDMD), leading to reduced pyroptosis and the accompanying inflammation. On the whole, the findings of the present study demonstrate that irisin attenuates ALI by inhibiting the HSP90/NLRP3/caspase‑1/GSDMD signaling pathway, reversing macrophage polarization and reducing the pyroptosis of macrophages. These findings provide a theoretical basis for understanding the role of irisin in the treatment of ALI and acute respiratory distress syndrome.

View Figures

View References

1	Wheeler AP and Bernard GR: Acute lung injury and the acute respiratory distress syndrome: A clinical review. Lancet. 369:1553–1564. 2007. View Article : Google Scholar : PubMed/NCBI
2	Zhou Z, Li X, Qian Y, Liu C, Huang X and Fu M: Heat shock protein 90 inhibitors suppress pyroptosis in THP-1 cells. Biochem J. 477:3923–3934. 2020. View Article : Google Scholar : PubMed/NCBI
3	Kovacs SB and Miao EA: Gasdermins: Effectors of pyroptosis. Trends Cell Biol. 27:673–684. 2017. View Article : Google Scholar :
4	Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F and Shao F: Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 526:660–665. 2015. View Article : Google Scholar : PubMed/NCBI
5	Fan EK and Fan J: Regulation of alveolar macrophage death in acute lung inflammation. Respir Res. 19:502018. View Article : Google Scholar : PubMed/NCBI
6	Martin WJ II, Wu M and Pasula R: A novel approach to restore lung immunity during systemic immunosuppression. Trans Am Clin Climatol Assoc. 116:221–227. 2005.
7	Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, Gordon S, Hamilton JA, Ivashkiv LB, Lawrence T, et al: Macrophage activation and polarization: Nomenclature and experimental guidelines. Immunity. 41:14–20. 2014. View Article : Google Scholar : PubMed/NCBI
8	Gordon S, Plüddemann A and Martinez Estrada F: Macrophage heterogeneity in tissues: Phenotypic diversity and functions. Immunol Rev. 262:36–55. 2014. View Article : Google Scholar : PubMed/NCBI
9	Xu J, Jiang Y, Wang J, Shi X, Liu Q, Liu Z, Li Y, Scott MJ, Xiao G, Li S, et al: Macrophage endocytosis of high-mobility group box 1 triggers pyroptosis. Cell Death Differ. 21:1229–1239. 2014. View Article : Google Scholar : PubMed/NCBI
10	Li Z, Scott MJ, Fan EK, Li Y, Liu J, Xiao G, Li S, Billiar TR, Wilson MA, Jiang Y and Fan J: Tissue damage negatively regulates LPS-induced macrophage necroptosis. Cell Death Differ. 23:1428–1447. 2016. View Article : Google Scholar : PubMed/NCBI
11	Yang J, Zhao Y, Zhang P, Li Y, Yang Y, Yang Y, Zhu J, Song X, Jiang G and Fan J: Hemorrhagic shock primes for lung vascular endothelial cell pyroptosis: Role in pulmonary inflammation following LPS. Cell Death Dis. 7:e23632016. View Article : Google Scholar : PubMed/NCBI
12	He X, Qian Y, Li Z, Fan EK, Li Y, Wu L, Billiar TR, Wilson MA, Shi X and Fan J: TLR4-upregulated IL-1β and IL-1RI promote alveolar macrophage pyroptosis and lung inflammation through an autocrine mechanism. Sci Rep. 6:316632016. View Article : Google Scholar
13	Mayor A, Martinon F, De Smedt T, Pétrilli V and Tschopp J: A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses. Nat Immunol. 8:497–503. 2007. View Article : Google Scholar : PubMed/NCBI
14	Davis BK, Wen H and Ting JP: The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu Rev Immunol. 29:707–735. 2011. View Article : Google Scholar : PubMed/NCBI
15	Piippo N, Korhonen E, Hytti M, Skottman H, Kinnunen K, Josifovska N, Petrovski G, Kaarniranta K and Kauppinen A: Hsp90 inhibition as a means to inhibit activation of the NLRP3 inflammasome. Sci Rep. 8:67202018. View Article : Google Scholar : PubMed/NCBI
16	Zhang M, Liu L, Lin X, Wang Y, Li Y, Guo Q, Li S, Sun Y, Tao X, Zhang D, et al: A translocation pathway for vesicle-mediated unconventional protein secretion. Cell. 181:637–652.e615. 2020. View Article : Google Scholar : PubMed/NCBI
17	Wu X and Rapoport TA: Mechanistic insights into ER-associated protein degradation. Curr Opin Cell Biol. 53:22–28. 2018. View Article : Google Scholar : PubMed/NCBI
18	Ruggiano A, Foresti O and Carvalho P: Quality control: ER-associated degradation: Protein quality control and beyond. J Cell Biol. 204:869–879. 2014. View Article : Google Scholar
19	Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT, Schneider BE and Mantzoros CS: FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism. 61:1725–1738. 2012. View Article : Google Scholar : PubMed/NCBI
20	Rabiee F, Lachinani L, Ghaedi S, Nasr-Esfahani MH, Megraw TL and Ghaedi K: New insights into the cellular activities of Fndc5/Irisin and its signaling pathways. Cell Biosci. 10:512020. View Article : Google Scholar : PubMed/NCBI
21	Xiong XQ, Geng Z, Zhou B, Zhang F, Han Y, Zhou YB, Wang JJ, Gao XY, Chen Q, Li YH, et al: FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK-mediated macrophage polarization in obesity. Metabolism. 83:31–41. 2018. View Article : Google Scholar : PubMed/NCBI
22	Mazur-Bialy AI, Pocheć E and Zarawski M: Anti-inflammatory properties of irisin, mediator of physical activity, are connected with TLR4/MyD88 signaling pathway activation. Int J Mol Sci. 18:7012017. View Article : Google Scholar : PubMed/NCBI
23	Shao L, Meng D, Yang F, Song H and Tang D: Irisin-mediated protective effect on LPS-induced acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells. Biochem Biophys Res Commun. 487:194–200. 2017. View Article : Google Scholar
24	National Research Council (NRC): Institute for laboratory animal research: Guide for the care and use of laboratory animals. 8th edition. National Academies Press; Washington, DC: 2011
25	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
26	Griffin RJ, Williams BW, Bischof JC, Olin M, Johnson GL and Lee BW: Use of a fluorescently labeled poly-caspase inhibitor for in vivo detection of apoptosis related to vascular-targeting agent arsenic trioxide for cancer therapy. Technol Cancer Res Treat. 6:651–654. 2007. View Article : Google Scholar : PubMed/NCBI
27	Cursio R, Colosetti P, Auberger P and Gugenheim J: Liver apoptosis following normothermic ischemia-reperfusion: In vivo evaluation of caspase activity by FLIVO assay in rats. Transplant Proc. 40:2038–2041. 2008. View Article : Google Scholar
28	Gill SE, Rohan M and Mehta S: Role of pulmonary microvascular endothelial cell apoptosis in murine sepsis-induced lung injury in vivo. Respir Res. 16:1092015. View Article : Google Scholar : PubMed/NCBI
29	Wang L, Lei W, Zhang S and Yao L: MCC950, a NLRP3 inhibitor, ameliorates lipopolysaccharide-induced lung inflammation in mice. Bioorg Med Chem. 30:1159542021. View Article : Google Scholar
30	Yokoyama S, Cai Y, Murata M, Tomita T, Yoneda M, Xu L, Pilon AL, Cachau RE and Kimura S: A novel pathway of LPS uptake through syndecan-1 leading to pyroptotic cell death. Elife. 7:e378542018. View Article : Google Scholar : PubMed/NCBI
31	Chen X, He WT, Hu L, Li J, Fang Y, Wang X, Xu X, Wang Z, Huang K and Han J: Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis. Cell Res. 26:1007–1020. 2016. View Article : Google Scholar :
32	Fink SL and Cookson BT: Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell Microbiol. 8:1812–1825. 2006. View Article : Google Scholar : PubMed/NCBI
33	Lv H, Liu Q, Wen Z, Feng H, Deng X and Ci X: Xanthohumol ameliorates lipopolysaccharide (LPS)-induced acute lung injury via induction of AMPK/GSK3β-Nrf2 signal axis. Redox Biol. 12:311–324. 2017. View Article : Google Scholar : PubMed/NCBI
34	Hughes KT and Beasley MB: Pulmonary manifestations of acute lung injury: More than just diffuse alveolar damage. Arch Pathol Lab Med. 141:916–922. 2017. View Article : Google Scholar
35	Nahrendorf M and Swirski FK: Abandoning M1/M2 for a network model of macrophage function. Circ Res. 119:414–417. 2016. View Article : Google Scholar :
36	Jiang R, Xu J, Zhang Y, Zhu X, Liu J and Tan Y: Ligustrazine alleviate acute lung injury through suppressing pyroptosis and apoptosis of alveolar macrophages. Front Pharmacol. 12:6805122021. View Article : Google Scholar : PubMed/NCBI
37	Benoit M, Desnues B and Mege JL: Macrophage polarization in bacterial infections. J Immunol. 181:3733–3739. 2008. View Article : Google Scholar : PubMed/NCBI
38	Man SM, Karki R and Kanneganti TD: Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol Rev. 277:61–75. 2017. View Article : Google Scholar : PubMed/NCBI
39	Frank D and Vince JE: Pyroptosis versus necroptosis: Similarities, differences, and crosstalk. Cell Death Differ. 26:99–114. 2019. View Article : Google Scholar
40	Sun X, Sun J, Dong B, Huang G, Zhang L, Zhou W, Lv J, Zhang X, Liu M, Xu L, et al: Noninvasive temperature monitoring for dual-modal tumor therapy based on lanthanide-doped up-conversion nanocomposites. Biomaterials. 201:42–52. 2019. View Article : Google Scholar : PubMed/NCBI
41	Aggarwal NR, King LS and D'Alessio FR: Diverse macrophage populations mediate acute lung inflammation and resolution. Am J Physiol Lung Cell Mol Physiol. 306:L709–L725. 2014. View Article : Google Scholar : PubMed/NCBI
42	He WT, Wan H, Hu L, Chen P, Wang X, Huang Z, Yang ZH, Zhong CQ and Han J: Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell Res. 25:1285–1298. 2015. View Article : Google Scholar : PubMed/NCBI
43	Luo D, Dai W, Feng X, Ding C, Shao Q, Xiao R, Zhao N, Peng W, Yang Y, Cui Y, et al: Suppression of lncRNA NLRP3 inhibits NLRP3-triggered inflammatory responses in early acute lung injury. Cell Death Dis. 12:8982021. View Article : Google Scholar : PubMed/NCBI
44	Coll RC, Robertson AA, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, et al: A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 21:248–255. 2015. View Article : Google Scholar : PubMed/NCBI