Inhibition of Synovial Hyperplasia, Rheumatoid T Cell Activation, and Experimental Arthritis in Mice by Sulforaphane, a Naturally Occurring Isothiocyanate
SCIE
SCOPUS
- Title
- Inhibition of Synovial Hyperplasia, Rheumatoid T Cell Activation, and Experimental Arthritis in Mice by Sulforaphane, a Naturally Occurring Isothiocyanate
- Authors
- Kong, JS; Yoo, SA; Kim, HS; Kim, HA; Yea, K; Ryu, SH; Chung, YJ; Cho, CS; Kim, WU
- Date Issued
- 2010-01
- Publisher
- WILEY-LISS
- Abstract
- Objective. To investigate whether sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables such as broccoli, regulates synoviocyte hyperplasia and T cell activation in rheumatoid arthritis (RA). Methods. Synoviocyte survival was assessed by MTT assay. The levels of Bcl-2, Bax, p53, and pAkt were determined by Western blot analysis. Cytokine concentrations in culture supernatants from mononuclear cells were analyzed by enzyme-linked immunosorbent assay. The in vivo effects of SFN were examined in mice with experimentally induced arthritis. Results. SFN induced synoviocyte apoptosis by modulating the expression of Bcl-2/Bax, p53, and pAkt. In addition, nonapoptotic doses of SFN inhibited T cell proliferation and the production of interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF alpha) by RA CD4+ T cells stimulated with anti-CD3 antibody. Anti-CD3 antibody-induced increases in the expression of retinoic acid-related orphan receptor gamma t and T-bet were also repressed by SFN. Moreover, the intraperitoneal administration of SFN to mice suppressed the clinical severity of arthritis induced by injection of type II collagen (CII), the anti-CII antibody levels, and the T cell responses to CII. The production of IL-17, TNF alpha, IL-6, and interferon-gamma by lymph node cells and spleen cells from these mice was markedly reduced by treatment with SFN. Anti-CII antibody-induced arthritis in mice was also alleviated by SFN injection. Conclusion. SFN was found to inhibit synovial hyperplasia, activated T cell proliferation, and the production of IL-17 and TNF alpha by rheumatoid T cells in vitro. The antiarthritic and immune regulatory effects of SFN, which were confirmed in vivo, suggest that SFN may offer a possible treatment option for RA.
- Keywords
- COLLAGEN-INDUCED ARTHRITIS; ENZYME-INDUCTION; GROWTH-FACTOR; CYCLE ARREST; CANCER RISK; II COLLAGEN; TNF-ALPHA; APOPTOSIS; EXPRESSION; IL-17
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/25686
- DOI
- 10.1002/ART.25017
- ISSN
- 0004-3591
- Article Type
- Article
- Citation
- ARTHRITIS AND RHEUMATISM, vol. 62, no. 1, page. 159 - 170, 2010-01
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