Interleukin-21 Induces Proliferation and Proinflammatory Cytokine Profile of Fibroblast-like Synoviocytes of Patients with Rheumatoid Arthritis.
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.
Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, China.
R
R
Xing
Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, China.
L
L
Yang
Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, China.
Y
Y
Jin
Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, China.
L
L
Sun
Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, China.
C
C
Li
Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, China.
Z
Z
Li
Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, China.
J
J
Zhao
Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing, 100191, China.
X
X
Liu
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D013583:Synovial Membrane / Q000276:immunology*; D000098546:Interleukin-21
D016207:Cytokines; D007378:Interleukins; D000098546:Interleukin-21