TY - JOUR T1 - Inhibition of Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Substrate-1 Reduces the Severity of Collagen-Induced Arthritis JF - The Journal of Rheumatology JO - J Rheumatol SP - 2316 LP - 2324 DO - 10.3899/jrheum.080369 VL - 35 IS - 12 AU - KONAGI TANAKA AU - TATSUYA HORIKAWA AU - SATSUKI SUZUKI AU - KAZUTAKA KITAURA AU - JUNKO WATANABE AU - AKITO GOTOH AU - NORIYUKI SHIOBARA AU - TSUNETOSHI ITOH AU - SHOJI YAMANE AU - RYUJI SUZUKI AU - NAOSHI FUKUI AU - TAKAHIRO OCHI Y1 - 2008/12/01 UR - http://www.jrheum.org/content/35/12/2316.abstract N2 - Objective To investigate whether the blockade of Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1) has any therapeutic effects on rheumatoid arthritis. Methods A functional blocking monoclonal antibody for SHPS-1 (anti-SHPS-1 mAb) was administered at various doses to collagen-induced arthritis (CIA) mice, and severity of the arthritis was evaluated by clinical and histological scores of the limbs. To clarify the mechanisms of action of the antibody, the serum concentration of anti-type II collagen antibody was measured in those mice, and in vitro experiments were conducted to determine the effects of the antibody on the induction of osteoclasts and the release of cytokines from mouse spleen cells. Results Compared with mice given control IgG, the administration of anti-SHPS-1 mAb significantly reduced the severity of inflammation and destruction of bone and cartilage in CIA mice. This therapeutic effect was observed even when the antibody treatment was started after the onset of arthritis. The appearance of anti-type II collagen antibody in CIA mice was not altered by the antibody treatment. In in vitro experiments, the anti-SHPS-1 mAb significantly inhibited osteoclastogenesis of bone marrow cells, and significantly reduced the release of interleukin 1β (IL-1β), IL-2, IL- 12, interferon-γ, and tumor necrosis factor-α, but not that of IL-4 or IL-10, from the spleen cells after stimulation with concanavalin A. Conclusion Administration of a monoclonal antibody for SHPS-1 reduced the severity of arthritis in CIA mice. Regulation of biological functions of SHPS-1 may be a novel and potent strategy to treat patients with rheumatoid arthritis. ER -