Transforming growth factor-beta stimulates IL-1beta-induced monocyte chemoattractant protein-1 expression in human synovial cells via the ERK/AP-1 pathway

Inflamm Res. 2006 Dec;55(12):543-9. doi: 10.1007/s00011-006-5144-9.

Abstract

Objective and design: Transforming growth factor- beta (TGF-beta) has not only a fibrogenic role, but also monocyte/ macrophage chemotactic properties in a synovial joint. However, little is known about the effects of TGF-beta on monocyte chemoattractant protein-1 (MCP-1) expression in human synovial cells under inflammatory status. The aim of this study was to determine whether TGF-modulates MCP-1 production under the chronic inflammation, and to elucidate the cell signaling mechanism involved.

Materials and methods: Human synovial cells were exposed to IL-1beta, which mimics the environment of chronic inflammation. Production of MCP-1 protein and expression of MCP-1 mRNA were determined by ELISA and real-time PCR.

Results: TGF-beta upregulated the expression of MCP-1 mRNA and protein with or without IL-1beta. TGF-beta and IL-1beta synergistically enhanced MCP-1 gene expression, and an AP-1 binding site was involved in the signal transduction. In addition, MEK inhibitor completely suppressed TGF-beta-induced MCP-1 production.

Conclusions: TGF-beta and IL-1beta synergistically enhance MCP-1 gene expression through the activation of the MEK/ERK1/2 pathways, which leads to AP-1 activation. The impairment of MCP-1 regulation by TGF-beta in resident synovial cells might represent an important mechanism of chronic inflammation and tissue fibrosis in a synovial joint. MCP-1 should be considered a valid target for therapeutic intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chemokine CCL2* / metabolism
  • Humans
  • Interleukin-1beta / metabolism
  • RNA, Messenger / metabolism
  • Transcription Factor AP-1 / metabolism
  • Transforming Growth Factor beta*
  • Transforming Growth Factors

Substances

  • Chemokine CCL2
  • Interleukin-1beta
  • RNA, Messenger
  • Transcription Factor AP-1
  • Transforming Growth Factor beta
  • Transforming Growth Factors