Expression and regulation of Toll-like receptor 2 in rheumatoid arthritis synovium.
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.
Seibl
Reinhart
R
Division for Immunology, Zurich University Children's Hospital, Zurich.
Birchler
Thomas
T
Loeliger
Susanne
S
Hossle
Johann Peter
JP
Gay
Renate E
RE
Saurenmann
Traudl
T
Michel
Beat A
BA
Seger
Reinhard A
RA
Gay
Steffen
S
Lauener
Roger P
RP
D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000473:pathology*; D001483:Base Sequence; D017931:DNA Primers; D029721:Drosophila Proteins; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics*; D010003:Osteoarthritis / Q000235:genetics / Q000473:pathology; D015347:RNA Probes; D011956:Receptors, Cell Surface / Q000235:genetics*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000166:cytology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D017931:DNA Primers; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D015347:RNA Probes; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors