NADPH quinone oxidoreductase induction by sulforaphane inhibits synovial hyperplasia and rheumatoid T cell proliferation. (50.15)

Abstract

Abstract Sulforaphane (SFN), derived from cruciferous vegetables, has been previously shown to induce phase II enzyme and to have anti-carcinogenic activity. In this study, we investigated whether SFN regulates synoviocyte hyperplasia and T cell proliferation in rheumatoid arthritis (RA). SFN induced synoviocyte apoptosis by regulating Bcl-2/Bax expression and pAkt activity. In addition, SFN dose-dependently inhibited T cell proliferation and the production of IL-17 and TNF-alpha by RA mononuclear cells stimulated with anti-CD3 antibody, but enhanced the enzyme activities of NADPH quinone oxidoreductase-1 (NQO1), a representative phase II enzyme. SFN inhibition of synoviocyte survival was abrogated by co-treatment with curcumin, an inhibitor of NQO1 or by downregulation of NQO1 transcripts. The intra-peritoneal administration of SFN to mice with type II collagen (CII)-induced arthritis suppressed arthritis severity, anti-CII antibody levels, and T cell proliferative response to CII. The productions of IL-17, TNF-alpha, IL-6, and IFN-gamma from lymph node and spleen cells of these mice also were markedly reduced by SFN treatment. Moreover, in mice with anti-CII antibody-induced arthritis, a passive model of arthritis that is independent of adaptive immunity, SFN treatment reduced arthritis severity and synovial hyperplasia. In summary, NQO1 induction by SFN was found to inhibit synoviocyte proliferation and TH17 cell activation in vitro. Moreover, the anti-arthritic and immune regulatory effects of SFN were confirmed in vivo, which suggests that SFN may offer a possible treatment option for RA.