IL-34 affects fibroblast-like synoviocyte proliferation, apoptosis and function by regulating IL-17
Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by proliferation and insufficient apoptosis of fibroblast-like synoviocytes (FLSs).The biology and functions of interleukin (IL)-34 are only beginning to be uncovered. We previously demonstrated IL-34 could upregulate...
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2021
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oai:doaj.org-article:2894796599fe4a90914b871836ba976a2021-12-02T18:50:47ZIL-34 affects fibroblast-like synoviocyte proliferation, apoptosis and function by regulating IL-1710.1038/s41598-021-95839-12045-2322https://doaj.org/article/2894796599fe4a90914b871836ba976a2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95839-1https://doaj.org/toc/2045-2322Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by proliferation and insufficient apoptosis of fibroblast-like synoviocytes (FLSs).The biology and functions of interleukin (IL)-34 are only beginning to be uncovered. We previously demonstrated IL-34 could upregulate the expression of IL-17 in RA patients. In this study, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry of Annexin V and PI staining were performed to assess cell proliferation and apoptosis progression in RA-FLSs after stimulated with increasing concentrations of IL-34, respectively. Inflammatory cytokines and angiogenic factors were measured using quantitative real-time PCR, Western blotting and ELISA. We explored the association between IL-34 and RA-FLS proliferation and apoptosis in the context of RA. Stimulating RA-FLSs with different concentrations of IL-34 significantly promoted the proliferation and inhibited the apoptosis of RA-FLSs in a concentration-dependent manner. Neutralization of IL-17 with the IL-17 inhibitor plumbagin (PB) reduced the effects of IL-34. Proinflammatory cytokine (IL-17A IL-6 and tumor necrosis factor-α, TNF-α) and angiogenic factor (vascular endothelial growth factor, VEGF and hypoxia-inducible factor-1α, HIF-1α) expression was markedly upregulated in RA-FLSs stimulated by IL-34. PB-mediated inhibition of IL-17A also decreased the expression of IL-6, TNF-α, HIF-1α and VEGF in RA-FLSs. Taken together, these findings suggest that targeting IL-34 production in RA-FLSs may be a therapeutic strategy for RA.Xin LiYimeng LeiZiyu GaoGang WuWei GaoLiping XiaJing LuHui ShenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
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Medicine R Science Q Xin Li Yimeng Lei Ziyu Gao Gang Wu Wei Gao Liping Xia Jing Lu Hui Shen IL-34 affects fibroblast-like synoviocyte proliferation, apoptosis and function by regulating IL-17 |
description |
Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by proliferation and insufficient apoptosis of fibroblast-like synoviocytes (FLSs).The biology and functions of interleukin (IL)-34 are only beginning to be uncovered. We previously demonstrated IL-34 could upregulate the expression of IL-17 in RA patients. In this study, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry of Annexin V and PI staining were performed to assess cell proliferation and apoptosis progression in RA-FLSs after stimulated with increasing concentrations of IL-34, respectively. Inflammatory cytokines and angiogenic factors were measured using quantitative real-time PCR, Western blotting and ELISA. We explored the association between IL-34 and RA-FLS proliferation and apoptosis in the context of RA. Stimulating RA-FLSs with different concentrations of IL-34 significantly promoted the proliferation and inhibited the apoptosis of RA-FLSs in a concentration-dependent manner. Neutralization of IL-17 with the IL-17 inhibitor plumbagin (PB) reduced the effects of IL-34. Proinflammatory cytokine (IL-17A IL-6 and tumor necrosis factor-α, TNF-α) and angiogenic factor (vascular endothelial growth factor, VEGF and hypoxia-inducible factor-1α, HIF-1α) expression was markedly upregulated in RA-FLSs stimulated by IL-34. PB-mediated inhibition of IL-17A also decreased the expression of IL-6, TNF-α, HIF-1α and VEGF in RA-FLSs. Taken together, these findings suggest that targeting IL-34 production in RA-FLSs may be a therapeutic strategy for RA. |
format |
article |
author |
Xin Li Yimeng Lei Ziyu Gao Gang Wu Wei Gao Liping Xia Jing Lu Hui Shen |
author_facet |
Xin Li Yimeng Lei Ziyu Gao Gang Wu Wei Gao Liping Xia Jing Lu Hui Shen |
author_sort |
Xin Li |
title |
IL-34 affects fibroblast-like synoviocyte proliferation, apoptosis and function by regulating IL-17 |
title_short |
IL-34 affects fibroblast-like synoviocyte proliferation, apoptosis and function by regulating IL-17 |
title_full |
IL-34 affects fibroblast-like synoviocyte proliferation, apoptosis and function by regulating IL-17 |
title_fullStr |
IL-34 affects fibroblast-like synoviocyte proliferation, apoptosis and function by regulating IL-17 |
title_full_unstemmed |
IL-34 affects fibroblast-like synoviocyte proliferation, apoptosis and function by regulating IL-17 |
title_sort |
il-34 affects fibroblast-like synoviocyte proliferation, apoptosis and function by regulating il-17 |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/2894796599fe4a90914b871836ba976a |
work_keys_str_mv |
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