Sulforaphane inhibits IL-1β-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of MMPs, COX-2, and PGE2

Inflammation. 2014 Oct;37(5):1496-503. doi: 10.1007/s10753-014-9875-4.

Abstract

This study was performed to define the effects of sulforaphane on interleukin-1β (IL-1β)-induced proliferation of rheumatoid arthritis synovial fibroblasts (RASFs), the expression of matrix metalloproteinases (MMPs) and cyclooxygenase (COX), and the production of prostaglandin E2 (PGE2) by RASFs. The proliferation of RASFs was evaluated with CCK-8 reagent in the presence of IL-1β with/without sulforaphane. The expression of MMPs, tissue inhibitor of metalloproteinase-1, COXs, intracellular mitogen-activated protein kinase signalings, including p-ERK, p-p38, p-JNK, and nuclear factor-kappaB (NF-kB), and the production of PGE2 were examined by Western blotting or semi-quantitative RT-PCR and ELISA. Sulforaphane inhibits unstimulated and IL-1β-induced proliferation of RASFs; the expression of MMP-1, MMP-3, and COX-2 mRNA and protein; and the PGE2 production induced by IL-1β. Sulforaphane also inhibits the phosphorylation of ERK-1/2, p-38, and JNK and activation of NF-kB by IL-1β. These results indicate that sulforaphane inhibits the proliferation of synovial fibroblasts, the expression of MMPs and COX-2, and the production of PGE2, which are involved in synovitis and destruction of RA, and suggest that sulforaphane might be a new therapeutic agent for RA.

MeSH terms

  • Arthritis, Rheumatoid / metabolism*
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Cyclooxygenase 2 / biosynthesis*
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / biosynthesis*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / pharmacology*
  • Isothiocyanates / pharmacology*
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 3 / biosynthesis*
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism

Substances

  • Interleukin-1beta
  • Isothiocyanates
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • MMP1 protein, human
  • Matrix Metalloproteinase 1
  • sulforaphane
  • Dinoprostone