IL-35 ameliorates collagen-induced arthritis by promoting TNF-α-induced apoptosis of synovial fibroblasts and stimulating M2 macrophages polarization.
FEBS J
; 286(10): 1972-1985, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-30834683
ABSTRACT
Synovitis, the chronic inflammation of the synovial membranes, is a hallmark of rheumatoid arthritis, a chronic disease with profound impact on human health. Recently, interleukin-35 (IL-35), a new member of the IL-12 family, was identified as an anti-inflammatory and immunosuppressive cytokine and was shown to ameliorate collagen-induced arthritis (CIA) in mice. However, the mechanism by which IL-35 alleviates CIA remains unknown. In this study, we investigated the effect of IL-35 on the CIA microenvironment and, specifically, the tumor necrosis factor alpha (TNF-α)-induced macrophage inflammatory response and apoptosis of fibroblast-like synoviocytes (FLSs). Firstly, using RT-PCR, western blot, and flow cytometry, we found that IL-35 suppressed TNF-α-induced inflammatory responses by down-regulating iNOS and COX-2 in peripheral blood monocyte-derived macrophages. IL-35 also activated alternative M2 macrophage polarization, as determined by evaluation of CCR7 and CD206 expression. Moreover, we showed that IL-35 enhanced TNF-α-induced FLS apoptosis. Using a panel of immunohistochemical and immunofluorescence analyses in a CIA model established in 18 DBA/1J mice, we demonstrated that IL-35 promotes synoviocyte apoptosis and alternative activation of macrophages to alleviate arthritis in vivo. Taken together, our results show that IL-35 promotes TNF-α-induced FLS apoptosis and modulates M2 macrophage polarization to ameliorate CIA inflammation both in vitro and in vivo.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Interleucinas
/
Fator de Necrose Tumoral alfa
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Macrófagos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article