Promotion of IL‑17/NF‑κB signaling in autoimmune thyroid diseases

Lu,Yamin; Xing,Chenhao; Zhang,Cuigai; Lv,Xiuqin; Liu,Guangxia; Chen,Fang; Hou,Zhan; Zhang,Donghui

doi:10.3892/etm.2022.11750

Promotion of IL‑17/NF‑κB signaling in autoimmune thyroid diseases

Authors:
- Yamin Lu
- Chenhao Xing
- Cuigai Zhang
- Xiuqin Lv
- Guangxia Liu
- Fang Chen
- Zhan Hou
- Donghui Zhang
View Affiliations

Affiliations: Department of Nuclear Medicine, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China, Department of Clinical Laboratory Diagnostics, Graduate School, Hebei North University, Zhangjiakou, Hebei 075000, P.R. China, Physical Examination Center, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China, Clinical Research Center, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
Published online on: December 6, 2022 https://doi.org/10.3892/etm.2022.11750
Article Number: 51
Copyright: © Lu 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

IL‑17 and other cytokines have a number of immunomodulatory effects on thyroid cells. The present study investigated the changes and correlations amongst IL‑17, NF‑κB, IL‑6, IL‑10, interferon‑γ (IFN‑γ), TNF‑α, IL‑2 and IL‑4 in patients with different autoimmune thyroid diseases in order to further clarify the pathogenesis of autoimmune thyroid disease. A total of 82 patients with autoimmune thyroid diseases (41 with Graves' disease and 41 with Hashimoto's thyroiditis) and 53 healthy controls were enrolled. All relevant thyroid hormones were detected by electrochemiluminescence analyzer. The serum levels of IL‑17 and other cytokines were detected using flow cytometry, NF‑κB was detected by ELISA, reverse transcription‑quantitative PCR was used to detect the protein expression of various mRNAs, and the correlations between IL‑17 and these factors were analyzed. Significant differences occurred amongst all groups. NF‑κB, TNF‑α, IL‑6, IL‑17 and their mRNA levels were significantly higher in the healthy controls compared with those in the patients; whereas IFN‑γ and IL‑10 levels were significantly lower in the healthy controls compared with those in the patients . Correlation analysis showed that the expression levels of IL‑17 and its mRNA were significantly positively correlated with the expression levels of NF‑κB, IL‑6, thyroid peroxidase antibody, thyroid gland globulin, thyroglobulin antibody, TNF‑α and IFN‑γ, and were also significantly negatively correlated with IL‑10 . These findings suggested that IL‑17 was elevated in patients with autoimmune thyroid disease and that IL‑17 could activate the NF‑κB signaling pathway, stimulate the production and release of inflammatory factors such as TNF‑α, IL‑6 and IFN‑γ and participate in the pathogenesis of autoimmune thyroid injury.

View Figures

View References

1	Rayman MP: Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease. Proc Nutr Soc. 78:34–44. 2018.PubMed/NCBI View Article : Google Scholar
2	Lei Y, Yang J, Li H, Zhong H and Wan Q: Changes in glucose-lipid metabolism, insulin resistance, and inflammatory factors in patients with autoimmune thyroid disease. J Clin Lab Anal. 33(e22929)2019.PubMed/NCBI View Article : Google Scholar
3	Dashdamirova G, Rahimova R, Baghirova S and Azizova U: Pathogenic mechanisms of autoimmune thyroid disease. Int J Med Sci Health Res. 06:26–33. 2022.
4	Barnabei L, Laplantine E, Mbongo W, Rieux-Laucat F and Weil R: NF-κB: At the borders of autoimmunity and inflammation. Front Immunol. 12(716469)2021.PubMed/NCBI View Article : Google Scholar
5	Capece D, Verzella D, Flati I, Arboretto P, Cornice J and Franzoso G: NF-κB: Blending metabolism, immunity, and inflammation. Trends Immunol. 43:757–775. 2022.PubMed/NCBI View Article : Google Scholar
6	Roberti A, Chaffey LE and Greaves DR: NF-κB Signaling and inflammation-drug repurposing to treat inflammatory disorders? Biology (Basel). 11(372)2022.PubMed/NCBI View Article : Google Scholar
7	Endocrine Society of Chinese Medical Association, Compilation group of《Guidelines for diagnosis and treatment of thyroid diseases in China》. Diagnosis and treatment of thyroid diseases in China-Laboratory and auxiliary examination of thyroid diseases. Chinese Journal of Internal Medicine,. 2007. 4:697–702. 2007.
8	Quintanal-Villalonga Á, Chan JM, Masilionis I, Gao VR, Xie Y, Allaj V, Chow A, Poirier JT, Pe'er D, Rudin CM and Mazutis L: Protocol to dissociate, process, and analyze the human lung tissue using single-cell RNA-seq. STAR Protoc. 3(101776)2022.PubMed/NCBI View Article : Google Scholar
9	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.PubMed/NCBI View Article : Google Scholar
10	Chimenz R, Tropeano A, Chirico V, Ceravolo G, Salpietro C and Cuppari C: IL-17 serum level in patients with chronic mucocutaneous candidiasis disease. Pediatr Allergy Immunol. 33 (Suppl 27):S77–S79. 2022.PubMed/NCBI View Article : Google Scholar
11	Zhang C, Chen J, Wang H, Chen J, Zheng MJ, Chen XG, Zhang L, Liang CZ and Zhan CS: IL-17 exacerbates experimental autoimmune prostatitis via CXCL1/CXCL2-mediated neutrophil infiltration. Andrologia. 54(e14455)2022.PubMed/NCBI View Article : Google Scholar
12	Zake T, Skuja S, Kalere I, Konrade I and Groma V: Heterogeneity of tissue IL-17 and tight junction proteins expression demonstrated in patients with autoimmune thyroid diseases. Medicine (Baltimore). 97(e11211)2018.PubMed/NCBI View Article : Google Scholar
13	Li S, Li S, Lin M, Li Z, He J, Qiu J and Zhang J: Interleukin-17 and vascular endothelial growth factor: New biomarkers for the diagnosis of papillary thyroid carcinoma in patients with Hashimoto's thyroiditis. J Int Med Res. 50(3000605211067121)2022.PubMed/NCBI View Article : Google Scholar
14	Hu S, Guo P, Wang Z, Zhou Z, Wang R, Zhang M, Tao J, Tai Y, Zhou W, Wei W and Wang Q: Down-regulation of A3AR signaling by IL-6-induced GRK2 activation contributes to Th17 cell differentiation. Exp Cell Res. 399(112482)2021.PubMed/NCBI View Article : Google Scholar
15	Esfahanian F, Ghelich R, Rashidian H and Jadali Z: Increased levels of serum interleukin-17 in patients with Hashimoto's thyroiditis. Indian J Endocrinol Metab. 21:551–554. 2017.PubMed/NCBI View Article : Google Scholar
16	Zake T, Kalere I, Upmale-Engela S, Svirskis S, Gersone G, Skesters A, Groma V and Konrade I: Plasma levels of Th17-associated cytokines and selenium status in autoimmune thyroid diseases. Immun Inflamm Dis. 9:792–803. 2021.PubMed/NCBI View Article : Google Scholar
17	Li Q, Wang B, Mu K and Zhang JA: The pathogenesis of thyroid autoimmune diseases: New T lymphocytes - Cytokines circuits beyond the Th1-Th2 paradigm. J Cell Physiol. 234:2204–2216. 2019.PubMed/NCBI View Article : Google Scholar
18	Li J, Zeng M, Yan K, Yang Y, Li H and Xu X: IL-17 promotes hepatocellular carcinoma through inhibiting apoptosis induced by IFN-γ. Biochem Biophys Res Commun. 522:525–531. 2020.PubMed/NCBI View Article : Google Scholar
19	Kristensen B: Regulatory B and T cell responses in patients with autoimmune thyroid disease and healthy controls. Dan Med J. 63(B5177)2016.PubMed/NCBI
20	Okda TM, Atwa GMK, Eldehn AF, Dahran N, Alsharif KF and Elmahallawy EK: A Novel role of galectin-3 and thyroglobulin in prognosis and differentiation of different stages of thyroid cancer and elucidation of the potential contribution of Bcl-2, IL-8 and TNF-α. Biomedicines. 10(352)2022.PubMed/NCBI View Article : Google Scholar
21	Wang J, Shi C, Chou G, Chen Z, Feng H and Wang S: Expression of TLR4, NF-κB and Treg/Th17 related cytokines in patients with Graves' Disease. Chinese Journal of Modern Medicine, 2017 Feb,. 27:58–61. 2017.
22	Lin SH, Ho JC, Li SC, Cheng YW, Hsu CY, Chou WY, Hsiao CC and Lee CH: TNF-α activating osteoclasts in patients with psoriatic arthritis enhances the recruitment of osteoclast precursors: A Plausible Role of WNT5A-MCP-1 in osteoclast engagement in psoriatic arthritis. Int J Mol Sci. 23(921)2022.PubMed/NCBI View Article : Google Scholar
23	Ma L, Jiang M, Zhao X, Sun J, Pan Q and Chu S: Cigarette and IL-17A synergistically induce bronchial epithelial-mesenchymal transition via activating IL-17R/NF-κB signaling. BMC Pulm Med. 20(26)2020.PubMed/NCBI View Article : Google Scholar
24	Wei L, Xiong H, Li W, Li B and Cheng Y: Upregulation of IL-6 expression in human salivary gland cell line by IL-17 via activation of p38 MAPK, ERK, PI3K/Akt, and NF-κB pathways. J Oral Pathol Med. 47:847–855. 2018.PubMed/NCBI View Article : Google Scholar
25	Salomon BL, Leclerc M, Tosello J, Ronin E, Piaggio E and Cohen JL: Tumor necrosis factor α and regulatory T cells in oncoimmunology. Front Immunol. 9(444)2018.PubMed/NCBI View Article : Google Scholar
26	Qi G, Zhu Y, Li Y, Li Y, Luo S and Li M: Role of NF-κB pathway in the pathogenesis of AITD. Journal of practical medicine, 2018 Oct. 34:3362–3366. 2018.
27	Zhao H, Chen W, Zhu L and Ge H: 1,25(OH)2D3 protects thyroid functions in experimental autoimmune thyroiditis rats by inhibiting the TLR2 / NF-κB signaling pathway. Chinese Journal of Comparative Medicine, 2022 Jan,. 32:78–86. 2022.
28	Zake T, Skuja S, Kalere I, Konrade I and Groma V: Upregulated tissue expression of T helper (Th) 17 pathogenic interleukin (IL)-23 and IL-1β in Hashimoto's thyroiditis but not in Graves' disease. Endocr J. 66:423–430. 2019.PubMed/NCBI View Article : Google Scholar
29	Pan Y, Wang M, Chen X, Chen Y, Ai S, Wang M, Su W and Liang D: Elevated IL-38 inhibits IL-23R expression and IL-17A production in thyroid-associated ophthalmopathy. Int Immunopharmacol. 91(107300)2021.PubMed/NCBI View Article : Google Scholar