Inhibition of synovial hyperplasia, rheumatoid T cell activation, and experimental arthritis in mice by sulforaphane, a naturally occurring isothiocyanate

Arthritis Rheum. 2010 Jan;62(1):159-70. doi: 10.1002/art.25017.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytokines / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / immunology
  • Fibroblasts / pathology
  • Humans
  • Hyperplasia / drug therapy
  • Hyperplasia / metabolism
  • Hyperplasia / pathology
  • Isothiocyanates
  • Leukocytes, Mononuclear
  • Lymph Nodes / drug effects
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymphocyte Activation / drug effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Spleen / drug effects
  • Spleen / metabolism
  • Spleen / pathology
  • Synovial Membrane / drug effects*
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology
  • Thiocyanates / pharmacology*

Substances

  • Antirheumatic Agents
  • Cytokines
  • Isothiocyanates
  • Thiocyanates
  • sulforaphane