Inhibition of synovial hyperplasia, rheumatoid T cell activation, and experimental arthritis in mice by sulforaphane, a naturally occurring isothiocyanate
Jin-Sun Kong
Catholic University of Korea, Seoul, South Korea
Ms Kong and Ms Yoo contributed equally to this work.
Search for more papers by this authorSeung-Ah Yoo
Catholic University of Korea, Seoul, South Korea
Ms Kong and Ms Yoo contributed equally to this work.
Search for more papers by this authorHyun Ah Kim
Hallym University Sacred Heart Hospital, Anyang, Kyunggi-do, South Korea
Search for more papers by this authorKyungmoo Yea
Pohang University of Science and Technology, Pohang, South Korea
Search for more papers by this authorSung-Ho Ryu
Pohang University of Science and Technology, Pohang, South Korea
Search for more papers by this authorYeun-Jun Chung
Catholic University of Korea, Seoul, South Korea
Search for more papers by this authorCorresponding Author
Wan-Uk Kim
Catholic University of Korea, Seoul, South Korea
Division of Rheumatology, Department of Internal Medicine, Catholic University of Korea, St. Vincent's Hospital, 93 Chi-Dong, Suwon 442-723, South KoreaSearch for more papers by this authorJin-Sun Kong
Catholic University of Korea, Seoul, South Korea
Ms Kong and Ms Yoo contributed equally to this work.
Search for more papers by this authorSeung-Ah Yoo
Catholic University of Korea, Seoul, South Korea
Ms Kong and Ms Yoo contributed equally to this work.
Search for more papers by this authorHyun Ah Kim
Hallym University Sacred Heart Hospital, Anyang, Kyunggi-do, South Korea
Search for more papers by this authorKyungmoo Yea
Pohang University of Science and Technology, Pohang, South Korea
Search for more papers by this authorSung-Ho Ryu
Pohang University of Science and Technology, Pohang, South Korea
Search for more papers by this authorYeun-Jun Chung
Catholic University of Korea, Seoul, South Korea
Search for more papers by this authorCorresponding Author
Wan-Uk Kim
Catholic University of Korea, Seoul, South Korea
Division of Rheumatology, Department of Internal Medicine, Catholic University of Korea, St. Vincent's Hospital, 93 Chi-Dong, Suwon 442-723, South KoreaSearch for more papers by this authorAbstract
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 α (TNFα) by RA CD4+ T cells stimulated with anti-CD3 antibody. Anti-CD3 antibody–induced increases in the expression of retinoic acid–related orphan receptor γt 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, TNFα, IL-6, and interferon-γ 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 TNFα 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.
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