Expression, modulation and signalling of IL-17 receptor in fibroblast-like synoviocytes of patients with rheumatoid arthritis

Clin Exp Immunol. 2002 Mar;127(3):539-46. doi: 10.1046/j.1365-2249.2002.01782.x.


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 to patients with osteoarthritis. In contrast to the restricted expression of IL-17, the IL-17 receptor (IL-17R/CDw217) is expressed ubiquitously. Using a real-time RT-PCR assay, we detected similar absolute levels of IL-17R mRNA expression in fibroblast-like synoviocytes (SFC) from patients with RA (mean 9 pg/microg total RNA; ranged from 0.1 pg to 96 pg IL-17R mRNA/microg total RNA) compared to synoviocytes of non-RA patients. Analysis of the IL-17R surface expression confirmed the results obtained for IL-17R mRNA expression. Exposure of SFC to IL-17 led to a mRNA induction of CXC chemokines IL-8, GRO-alpha and GRO-beta. An anti-IL-17 antibody blocked these effects of IL-17. The MAPK p38 appears necessary for the regulation of IL-8, GRO-alpha and GRO-beta expression as shown by inhibition with SB203580. The inhibitors genistein (tyrosine kinase inhibitor) and calphostin C (inhibitor of protein kinase C) reduced significantly the IL-17-stimulated mRNA expression of IL-8, GRO-alpha and GRO-beta in SFC, whereas PD98059 (inhibitor of MEK-1/2) was without effect. Pharmacological drugs used in therapy of RA, such as cyclosporin and methotrexate, induced a fourfold increase of IL-17R mRNA expression and augmented the IL-17-stimulated IL-8 expression. Our results support the hypothesis that IL-17/IL-17R may play a significant role in the pathogenesis of RA contributing to an unbalanced production of cytokines as well as participating in connective tissue remodelling.

Publication types

  • Comparative Study

MeSH terms

  • Antirheumatic Agents / pharmacology
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Cells, Cultured
  • Chemokine CXCL1
  • Chemokines, CXC*
  • Chemotactic Factors / biosynthesis
  • Chemotactic Factors / genetics
  • Cyclosporine / pharmacology
  • Fibroblasts / drug effects
  • Fibroblasts / immunology*
  • Growth Substances / biosynthesis
  • Growth Substances / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Interleukin-17 / pharmacology
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Kinetics
  • MAP Kinase Signaling System
  • Methotrexate / pharmacology
  • NF-kappa B / metabolism
  • RNA, Messenger / biosynthesis
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-17
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*
  • Signal Transduction*
  • Synovial Membrane / cytology
  • Synovial Membrane / immunology*
  • Transcription, Genetic
  • U937 Cells


  • Antirheumatic Agents
  • CXCL1 protein, human
  • Chemokine CXCL1
  • Chemokines, CXC
  • Chemotactic Factors
  • Growth Substances
  • IL17RA protein, human
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-17
  • Interleukin-8
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-17
  • Recombinant Proteins
  • Cyclosporine
  • Methotrexate