Toll-like receptors and rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic inflammatory disease that ultimately leads to the progressive destruction of cartilage and bone in numerous joints. There is mounting evidence for an important function of innate immunity in the pathogenesis of RA. Activation of cells by microbial components and also by endogenous molecules via Toll-like receptor (TLR) results in the production of a variety of proinflammatory cytokines, chemokines, and destructive enzymes, some of which can characteristically be found in RA.By immunohistochemistry we found elevated TLR2, 3, and 4 expressions in the rheumatoid synovium. In the synovial lining layer and at sites of invasion into cartilage, RA synovial fibroblasts (RASF) are the major cells expressing TLR2, 3, and 4. Stimulation of cultured RASF in vitro with the TLR2 ligand bacterial lipoprotein (bLP), the TLR3 ligand poly(I-C), and the TLR4 ligand LPS was shown to upregulate IL-6 as well as matrix metalloproteinases (MMPs) 1 and 3. These results suggest an important role for TLR2, 3, and 4 in the activation of synovial fibroblasts in RA leading to chronic inflammation and joint destruction.
Brentano
Fabia
F
Department of Rheumatology, University Hospital Zürich, Gloriastrasse 25, CH-8091 Zurich, Switzerland.
Kyburz
Diego
D
Gay
Steffen
S
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005629:Frozen Sections; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D016133:Polymerase Chain Reaction; D012313:RNA / Q000302:isolation & purification; D051193:Toll-Like Receptors / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*
D015850:Interleukin-6; D008024:Ligands; D051193:Toll-Like Receptors; D012313:RNA