Source:http://linkedlifedata.com/resource/pubmed/id/17330802
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2007-3-2
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| pubmed:abstractText |
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.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin beta Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/VCL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vinculin
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
1699-5848
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
22
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
469-82
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:17330802-Aged,
pubmed-meshheading:17330802-Apoptosis,
pubmed-meshheading:17330802-Blotting, Western,
pubmed-meshheading:17330802-Cartilage, Articular,
pubmed-meshheading:17330802-Caspase 3,
pubmed-meshheading:17330802-Cell Shape,
pubmed-meshheading:17330802-Cells, Cultured,
pubmed-meshheading:17330802-Chondrocytes,
pubmed-meshheading:17330802-Collagen Type II,
pubmed-meshheading:17330802-Cyclooxygenase 2,
pubmed-meshheading:17330802-Dose-Response Relationship, Drug,
pubmed-meshheading:17330802-Fibronectins,
pubmed-meshheading:17330802-Humans,
pubmed-meshheading:17330802-Integrin beta Chains,
pubmed-meshheading:17330802-Interleukin-18,
pubmed-meshheading:17330802-MAP Kinase Signaling System,
pubmed-meshheading:17330802-Membrane Proteins,
pubmed-meshheading:17330802-Microscopy, Electron, Transmission,
pubmed-meshheading:17330802-Microscopy, Fluorescence,
pubmed-meshheading:17330802-Middle Aged,
pubmed-meshheading:17330802-Mitogen-Activated Protein Kinases,
pubmed-meshheading:17330802-Time Factors,
pubmed-meshheading:17330802-Vinculin
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| pubmed:year |
2007
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| pubmed:articleTitle |
Interleukin-18 induces apoptosis in human articular chondrocytes.
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| pubmed:affiliation |
Department of Trauma and Reconstructive Surgery, Charité University Medical School, Campus Benjamin Franklin, Berlin, Germany. thilo.john@charite.de
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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