Inhibition of Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 reduces the severity of collagen-induced arthritis

Konagi Tanaka, Tatsuya Horikawa, Satsuki Suzuki, Kazutaka Kitaura, Junko Watanabe, Akito Gotoh, Noriyuki Shiobara, Tsunetoshi Itoh, Shoji Yamane, Ryuji Suzuki, Naoshi Fukui, Takahiro Ochi

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2316-2324
Number of pages9
JournalJournal of Rheumatology
Volume35
Issue number12
DOIs
Publication statusPublished - 2008 Dec

Keywords

  • Rheumatoid arthritis
  • SHPS-1
  • Therapeutics

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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