Acacetin inhibits expression of matrix metalloproteinases via a MAPK-dependent mechanism in fibroblast-like synoviocytes

J Cell Mol Med. 2015 Aug;19(8):1910-5. doi: 10.1111/jcmm.12564. Epub 2015 Apr 9.

Abstract

It is well known that rheumatoid arthritis (RA) is an autoimmune joint disease in which fibroblast-like synoviocytes (FLSs) play a pivotal role. In this study, we investigated the anti-arthritic properties of acacetin in FLSs. The expression of matrix metalloproteinase (MMP)-1, MMP-3 and MMP-13 were investigated by quantitative RT-PCR and western blot at gene and protein levels. At the same time, the phosphorylation of mitogen-activated protein kinases (MAPK) was investigated. The DNA-binding activity of NF-κB was investigated by electrophoretic mobility shift assay. We found that acacetin inhibits p38 and JNK phosphorylation and reduces MMP-1, MMP-3 and MMP-13 expression in interleukin-1β-induced FLSs. Our results suggest that acacetin has antiarthritic effects in FLSs. Thus, acacetin should be further studied for the treatment of arthritis.

Keywords: acacetin; fibroblast-like synoviocytes; interleukin-1β; matrix metalloproteinase; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • DNA / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology*
  • Flavones / pharmacology*
  • Humans
  • Interleukin-1beta / pharmacology
  • Interleukin-6 / biosynthesis
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinases / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • Synovial Membrane / cytology*

Substances

  • Flavones
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • DNA
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 1
  • acacetin

Associated data

  • GENBANK/J03209
  • RefSeq/NM_002046
  • RefSeq/NM_002421
  • RefSeq/NM_002427