TNF-alpha induces the transcription factor Egr-1, pro-inflammatory cytokines and cell proliferation in human skin fibroblasts and synovial lining cells

Rheumatol Int. 1998;17(5):185-92. doi: 10.1007/s002960050032.

Abstract

In rheumatoid arthritis (RA) cell proliferation and altered metalloproteinase expression of synovial lining cells are associated with increased levels of TNF-alpha in the rheumatoid joint. We previously showed that synoviocytes of RA patients express high levels of the transcription factor Egr-1. Here we report that TNF-alpha is capable of inducing high Egr-1 mRNA levels in human skin fibroblasts and in synoviocytes from both, RA and reactive arthritis patients. Moreover, we observed in vitro a marked increase in fibroblast proliferation, a loss of growth inhibition by cell-to-cell contact with pannus-like cell growth and an altered cytokine expression pattern when synoviocytes were cultured in presence of TNF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / drug effects
  • Cells, Cultured
  • Cytokines / drug effects*
  • Cytokines / genetics
  • DNA-Binding Proteins / drug effects*
  • DNA-Binding Proteins / genetics
  • Early Growth Response Protein 1
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Humans
  • Immediate-Early Proteins*
  • Male
  • Skin / cytology
  • Skin / drug effects
  • Synovial Membrane / chemistry
  • Synovial Membrane / cytology
  • Synovial Membrane / drug effects*
  • Transcription Factors / drug effects*
  • Transcription Factors / genetics
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Cytokines
  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Immediate-Early Proteins
  • Transcription Factors
  • Tumor Necrosis Factor-alpha