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Interleukin-18 induces apoptosis in human articular chondrocytes

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dc.contributor.authorJohn, T.es
dc.contributor.authorKohl, B.es
dc.contributor.authorMobasheri, A.
dc.contributor.authorErtel, W.
dc.contributor.authorShakibaei, M.
dc.date.accessioned2012-05-21T12:09:32Z
dc.date.available2012-05-21T12:09:32Z
dc.date.issued2007
dc.description.abstractElevated 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 ß-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 IIdeposition, decreased ß-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 cartilagespecific cartilagespecific 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.es
dc.formatapplication/pdfes
dc.format.extent14es
dc.identifier.issn0213-3911es
dc.identifier.urihttp://hdl.handle.net/10201/27583
dc.languageenges
dc.publisherMurcia : F. Hernándezes
dc.relation.ispartofHistology and histopathologyes
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.subjectApoptosises
dc.subjectChondrocytees
dc.subject.other617 - Cirugía. Ortopedia. Oftalmologíaes
dc.titleInterleukin-18 induces apoptosis in human articular chondrocyteses
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.22, nº 5 (2007)