IL-32 aggravates synovial inflammation and bone destruction and increases synovial natural killer cells in experimental arthritis models.

This study was performed to investigate the effects of IL-32 on joint inflammation, bone destruction, and synovial cytokine expressions, and on synovial natural killer (NK) cell expressions in collagen-induced arthritis (CIA). CIA was induced by type II collagen in DBA1 mice, and phosphate-buffered saline (PBS group) or IL-32 (IL-32 group) were injected into both knee joints at day 28 and 32, then mice were killed at day 35. Severity of synovial inflammation and bone destruction was determined by histological scoring method, and synovial cytokine expressions such as IL-1ß, TNF-α, IL-17, IL-18, IFN-γ, IL-21, and IL-23 were measured by real-time RT-PCR and western blot. Synovial NK cell expressions were determined by real-time RT-PCR, western blot and immunohistochemistry, and chemokines and chemokine receptors expressions that are associated with NK cell migration were determined by real-time RT-PCR. Scores of synovial inflammation and bone destruction, synovial expressions of IL-1ß, TNF-α, IL-18, and IFN-γ were significantly increased in IL-32 group compared with PBS group. Synovial expressions of NK cell, and chemokines (CCL2 and CXCL9) and chemokine receptors (CCR2 and CCR5) that are associated with NK cell migration were significantly increased in IL-32 group compared with PBS group. IL-32 aggravated joint inflammation and bone destruction and increased synovial expressions of inflammatory cytokine and NK cells in CIA. These results suggest that IL-32 play a role in joint inflammation and bone destruction, and IL-32 might be a new target for treatment of rheumatoid arthritis.

IL-17 increases cadherin-11 expression in a model of autoimmune experimental arthritis and in rheumatoid arthritis.

IL-17 plays important roles in synovial inflammation and bone destruction in the mouse model of autoimmune arthritis and in rheumatoid arthritis (RA). Cadherin-11 determines the behavior of synovial cells in their proinflammatory and destructive tissue response in inflammatory arthritis, and promotes the invasive behavior of fibroblast-like synoviocytes (FLS). The purpose of this study was to examine the effect of IL-17 on the expression of cadherin-11 in autoimmune experimental arthritis and in RA synovium. The severity of synovial inflammation and bone destruction were examined in IL-17-injected knee joints of mice with collagen-induced arthritis (CIA). Cadherin-11 expression was examined in the synovium of mice with CIA, of IL-1 receptor antagonist (IL-1Ra)-deficient mice and of patients with RA and osteoarthritis (OA). Cadherin-11 expression was also examined in the synovium of IL-17 injected knee joints from CIA mice and in IL-17-stimulated FLS of CIA mice and RA patients. IL-17 aggravated synovial inflammation and bone destruction in CIA. By immunohistochemistry, cadherin-11 expression was increased in the synovium of mice with CIA and IL-1Ra-deficient mice and in patients with RA. Synovial cadherin-11 expression in IL-17-injected knee joints, measured by real-time RT-PCR, Western blot and immunohistochemistry, was increased in CIA. Cadherin-11 expression was significantly increased by IL-17 in cultured FLS of CIA mice and RA patients, and these increases were blocked by NF-κB inhibitors. IL-17 increased the expression of cadherin-11 in vivo and in vitro, which implies that an IL-17-induced increase of cadherin-11 is involved in IL-17-induced aggravation of joint destruction and inflammation.