Interleukin‐21 Induces Proliferation and Proinflammatory Cytokine Profile of Fibroblast‐like Synoviocytes of Patients with Rheumatoid Arthritis |
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| Authors: | R. Xing L. Yang Y. Jin L. Sun C. Li Z. Li J. Zhao X. Liu |
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| Affiliation: | 1. Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, China;2. Department of Anesthesiology, Peking University Third Hospital, Beijing, China |
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| Abstract: | Fibroblast‐like synoviocytes (FLS) play a pivotal role in the pathogenesis of rheumatoid arthritis (RA) through aggressive proliferation and invasion, and certain proinflammatory cytokines may affect synoviocyte proliferation. To evaluate whether interleukin‐21 (IL‐21) could promote proliferation and proinflammatory cytokine production by RA‐FLS, immunohistochemistry and immunoblotting were performed to observe the expression of IL‐21 receptor (IL‐21R) in synovial tissues and FLS from RA and osteoarthritis (OA) patients. The MTS assay was used to analyse RA‐FLS proliferation. The concentrations of IL‐6 and tumour necrosis factor‐α (TNF‐α) in culture supernatants were determined by enzyme‐linked immunosorbent assay (ELISA). The signalling pathways triggered by IL‐21 were characterized by immunoblotting. IL‐21R was upregulated in the synovial tissues and FLS of RA patients as compared with OA patients. IL‐21 stimulated RA‐FLS proliferation and promoted the production of TNF‐α and IL‐6 and blockade of IL‐21/IL‐21R pathway with IL‐21R.Fc attenuated IL‐21‐induced proliferation and secretion of TNF‐α and IL‐6. Moreover, IL‐21 induced activation of the ERK1/2, PI3K/AKT and STAT3 pathways, and blockade of these pathways attenuated IL‐21‐induced proliferation and secretion of TNF‐α and IL‐6. These results suggest that IL‐21 could promote RA‐FLS proliferation and production of proinflammatory cytokines. Therefore, therapeutic strategies targeting IL‐21 might be effective for the treatment of RA. |
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