Gene expression induced by interleukin-17 in fibroblast-like synoviocytes of patients with rheumatoid arthritis: upregulation of hyaluronan-binding protein TSG-6

Arthritis Res Ther. 2003;5(4):R186-92. doi: 10.1186/ar762. Epub 2003 Apr 28.


Interleukin-17 (IL-17) has been characterized as a proinflammatory cytokine produced by CD4+ CD45RO+ memory T cells. Overproduction of IL-17 was detected in the synovium of patients with rheumatoid arthritis (RA) compared with patients with osteoarthritis. This study examines differentially expressed genes after the stimulation of fibroblast-like synoviocytes of RA patients by IL-17. Among these genes we identified the following: tumor necrosis factor-stimulated gene-6 (TSG-6), IL-6, IL-8, GRO-beta, and bone morphogenetic protein-6 with an expression 3.6-10.6-fold that in the unstimulated control. IL-17 augmented the expression of TSG-6, a hyaluronan-binding protein, in a time- and dose-dependent manner. IL-17 showed additive effects with IL-1beta and tumour necrosis factor-alpha on the expression of TSG-6, IL-6 and IL-8. The mitogen-activated protein kinase p38 seems to be necessary for the regulation of TSG-6 expression by IL-17, as shown by inhibition with SB203580. Our results support the hypothesis that IL-17 is important in the pathogenesis of RA, contributing to an unbalanced production of cytokines as well as participating in connective tissue remodeling.

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / metabolism*
  • Cell Adhesion Molecules / biosynthesis*
  • Cell Adhesion Molecules / genetics
  • Cells, Cultured
  • Drug Synergism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Humans
  • Hyaluronic Acid / metabolism
  • Interleukin-1 / pharmacology
  • Interleukin-17 / pharmacology*
  • Interleukin-6 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Middle Aged
  • Synovial Membrane / cytology
  • Synovial Membrane / metabolism*
  • Transcriptional Activation
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation


  • Cell Adhesion Molecules
  • Interleukin-1
  • Interleukin-17
  • Interleukin-6
  • Interleukin-8
  • TNFAIP6 protein, human
  • Tumor Necrosis Factor-alpha
  • Hyaluronic Acid