title: Inhibition of synovial hyperplasia, rheumatoid T cell activation, and experimental arthritis in mice by sulforaphane, a naturally occurring isothiocyanate.
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 (TNFalpha) by RA CD4+ T cells stimulated with anti-CD3 antibody. Anti-CD3 antibody-induced increases in the expression of retinoic acid-related orphan receptor gammat 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, TNFalpha, 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.
  
  
  CONCLUSIONS
  SFN was found to inhibit synovial hyperplasia, activated T cell proliferation, and the production of IL-17 and TNFalpha 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.
authors.affiliation: Catholic University of Korea, Seoul, South Korea.
authors.forename: Jin-Sun
authors.initials: JS
authors.lastname: Kong
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Yoo
authors.forename: Hyun-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Kim
authors.forename: Kyungmoo
authors.initials: K
authors.lastname: Yea
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Yeun-Jun
authors.initials: YJ
authors.lastname: Chung
authors.forename: Chul-Soo
authors.initials: CS
authors.lastname: Cho
authors.forename: Wan-Uk
authors.initials: WU
authors.lastname: Kim
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017879:Isothiocyanates; D007963:Leukocytes, Mononuclear; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013454:Sulfoxides; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D013861:Thiocyanates / Q000494:pharmacology*
chemical_list: D018501:Antirheumatic Agents; D016207:Cytokines; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane