Expression of interleukin-18 receptor in fibroblast-like synoviocytes

Arthritis Res. 2002;4(2):139-44. doi: 10.1186/ar390. Epub 2001 Nov 14.

Abstract

An excess of the proinflammatory substance IL-18 is present in joints of patients with rheumatoid arthritis (RA), and expression of IL-18 receptor (IL-18R) regulates IL-18 bioactivity in various cell types. We examined the expression of IL-18R alpha-chain and beta-chain and the biologic effects of IL-18 in fibroblast-like synoviocytes (FLS) after long-term culture. The presence of both IL-18R chains was a prerequisite for IL-18 signal transduction in FLS. However, all FLS cultures studied were either resistant or barely responsive to IL-18 stimulation as regards cell proliferation, expression of adhesion molecules ICAM-1 and vascular cell adhesion molecule (VCAM)-1, and the release of interstitial collagenase and stromelysin, IL-6 and IL-8, prostaglandin E2, or nitric oxide. We conclude that the presence of macrophages or IL-18R+ T cells that can respond directly to IL-18 is essential for the proinflammatory effects of IL-18 in synovitis in RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Cell Division / drug effects
  • Cells, Cultured
  • Collagenases / metabolism
  • Culture Media, Conditioned / metabolism
  • Dinoprostone / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-18 / metabolism
  • Interleukin-18 / pharmacology
  • Interleukin-18 Receptor alpha Subunit
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Nitric Oxide / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-18
  • Signal Transduction
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism*
  • Synovial Membrane / pathology
  • U937 Cells / drug effects
  • U937 Cells / metabolism
  • U937 Cells / pathology
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Culture Media, Conditioned
  • IL18R1 protein, human
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Interleukin-6
  • Interleukin-8
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-18
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Nitric Oxide
  • Collagenases
  • Matrix Metalloproteinase 3
  • Dinoprostone