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• W54194632 endingPage "82" @default.
• W54194632 startingPage "469" @default.
• W54194632 abstract "Elevated levels of the pro-inflammatory cytokine, interleukin-18 (IL-18) have recently been demonstrated in osteoarthritic cartilage. However, the effects of IL-18 on chondrocyte signalling and matrix biosynthesis are poorly understood. Therefore, the present study was undertaken to further characterize the impact of IL-18 on human articular chondrocyte in vitro. Human articular chondrocytes were stimulated with various concentrations of recombinant human IL-18 (1, 10, 100 ng/ml) for 0, 4, 8, 12, 24, 48, 72 h in vitro. The effects of IL-18 on the cartilage-specific matrix protein collagen type II, the cytoskeletal protein vinculin, the cell matrix signal transduction receptor beta-integrin, key signalling proteins of the MAPKinase pathway (such as SHC (Sarc Homology Collagen) and activated MAPKinase [ERK-1/-2]), the pro-inflammatory enzyme cyclo-oxygenase-2 (COX-2) and the apoptosis marker activated caspase-3 were evaluated by Western blot analysis and immunofluorescence labelling. Morphological features of IL-18 stimulated chondrocytes were estimated by transmission electron microscopy. IL-18 lead to inhibition of collagen type II-deposition, decreased beta-integrin receptor and vinculin synthesis, SHC and MAPKinase activation, increased COX-2 synthesis and activation of caspase-3 in chondrocytes in a time- and dose-dependent manner. Furthermore, chondrocytes treated with IL-18 exhibited typical morphological features of apoptosis as revealed by transmission electron microscopy. Taken together, the results of the present study underline key catabolic events mediated by IL-18 signalling in chondrocytes such as loss of cartilage-specific matrix and apoptosis. Inhibition of MAPKinase signalling is hypothesized to contribute to these features. Future therapeutics targeting IL-18 signalling pathways may be beneficial in rheumatoid arthritis and osteoarthritis therapy." @default.
• W54194632 created "2016-06-24" @default.
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• W54194632 date "2007-05-01" @default.
• W54194632 modified "2023-10-01" @default.
• W54194632 title "Interleukin-18 induces apoptosis in human articular chondrocytes." @default.
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• W54194632 doi "https://doi.org/10.14670/hh-22.469" @default.
• W54194632 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17330802" @default.
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