Expression of proteinase-activated receptors (PAR)-2 in articular chondrocytes is modulated by IL-1beta, TNF-alpha and TGF-beta.
OBJECTIVE
To investigate the modulation of expression of proteinase-activated receptor-2 (PAR-2) in articular chondrocytes by inflammatory cytokines.


METHODS
Articular synovium and cartilage tissues were collected from eight patients with osteoarthritis (OA), and three patients without arthropathy ("normal"). Chondrocytes were stimulated with interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha or transforming growth factor (TGF)-beta1. The expression of PAR-2 was detected using reverse transcriptase-polymerase chain reaction (PCR), Western blotting and immunofluorescence. Quantitative PCR was performed to assess the expression levels of PAR-2 messenger RNA (mRNA).


RESULTS
The expression of PAR-2 mRNA was demonstrated in both OA and normal chondrocytes as well as in synovial fibroblasts. However, the level of PAR-2 in OA chondrocytes was much higher than in normal chondrocytes. Long-term culture revealed that PAR-2 mRNA expression was maintained up to three passages in OA but not in normal chondrocytes. IL-1beta and TNF-alpha both upregulated PAR-2 expression in normal and OA chondrocytes. In contrast, TGF-beta1 significantly decreased expression of PAR-2 in OA chondrocytes but increased PAR-2 in normal chondrocytes.


CONCLUSIONS
Overexpression of PAR-2 in OA chondrocytes is upregulated by proinflammatory cytokines IL-1beta and TNF-alpha, and down-regulated by regulatory cytokine TGF-beta1. PAR-2 may be involved in the pathogenesis of OA.
Xiang
Y
Y
Department of Bioregulation and Proteomics, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
Masuko-Hongo
K
K
Sekine
T
T
Nakamura
H
H
Yudoh
K
K
Nishioka
K
K
Kato
T
T
D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000276:immunology*; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D003593:Cytoplasm / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D044464:Receptor, PAR-2 / Q000032:analysis*; D013583:Synovial Membrane / Q000276:immunology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D016207:Cytokines; D053583:Interleukin-1beta; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha