Expression and Regulation of Toll-like Receptor 2 in Rheumatoid Arthritis Synovium

Am J Pathol. 2003 Apr;162(4):1221-7. doi: 10.1016/S0002-9440(10)63918-1.

Abstract

Toll-like receptors (TLRs) are involved in mediating cell activation on stimulation with microbial constituents. We investigated the role for TLRs in synovial fibroblast (SF) activation in rheumatoid arthritis (RA). We analyzed whether stimulation with interleukin-1 beta and tumor necrosis factor-alpha, cytokines present in RA synovium, influences expression of TLR genes in SFs. The effects were compared with those of treatment with lipopolysaccharide and a synthetic lipopeptide (sBLP). Gene expression was examined using quantitative polymerase chain reaction. TLR2-mediated cell activation was investigated by electromobility shift assay for nuclear factor-kappa B. To localize TLR2 expression in joint tissue sections of RA patients were stained using in situ hybridization. Expression of TLR2 in RA SFs was increased after treatment with interleukin-1 beta, tumor necrosis factor-alpha, lipopolysaccharide, and sBLP. Nuclear factor-kappa B translocation in SFs was triggered by TLR2-mediated cell stimulation. Synovial tissues from RA joints expressed TLR2 predominantly at sites of attachment and invasion into cartilage and bone. The observed elevated expression of TLR2 in RA SFs could be a consequence of direct exposure to microbial compounds or of the presence of inflammatory mediators in the joint. TLR-associated signaling pathways may contribute to the pathogenesis of RA, either by initiating or perpetuating activation of SFs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / pathology*
  • Base Sequence
  • DNA Primers
  • Drosophila Proteins*
  • Fibroblasts / immunology
  • Fibroblasts / pathology
  • Gene Expression Regulation* / physiology*
  • Humans
  • Immunohistochemistry
  • Macrophages / immunology
  • Macrophages / pathology
  • Membrane Glycoproteins / genetics*
  • Osteoarthritis / genetics
  • Osteoarthritis / pathology
  • RNA Probes
  • Receptors, Cell Surface / genetics*
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synovial Membrane / cytology
  • Synovial Membrane / pathology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Toll-Like Receptor 2
  • Toll-Like Receptors

Substances

  • DNA Primers
  • Drosophila Proteins
  • Membrane Glycoproteins
  • RNA Probes
  • Receptors, Cell Surface
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptors