Source:http://linkedlifedata.com/resource/pubmed/id/11319753
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2001-4-25
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| pubmed:abstractText |
We have previously shown that p38 mitogen-activated protein kinase (MAPK) inhibitors, which block the production and action of inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1), are effective in models of bone and cartilage degradation. To further investigate the role of p38 MAPK, we have studied its activation in osteoblasts and chondrocytes, following treatment with a panel of proinflammatory and osteotropic agents. In osteoblasts, significant activation of p38 MAPK was observed following treatment with IL-1 and TNF, but not parathyroid hormone, transforming growth factor-beta (TGF-beta), 1,25(OH)(2)D(3), insulin-like growth factor-1 (IGF-1), or IGF-II. Similar results were obtained using primary bovine chondrocytes and an SV40-immortalized human chondrocyte cell line, T/C28A4. SB 203580, a selective inhibitor of p38 MAPK, inhibited IL-1 and TNF-induced p38 MAPK activity and IL-6 production (IC(50)s 0.3--0.5 microM) in osteoblasts and chondrocytes. In addition, IL-1 and TNF also activated p38 MAPK in fetal rat long bones and p38 MAPK inhibitors inhibited IL-1- and TNF-stimulated bone resorption in vitro in a dose-dependent manner (IC(50)s 0.3--1 microM). These data support the contention that p38 MAPK plays a central role in regulating the production of, and responsiveness to, proinflammatory cytokines in bone and cartilage. Furthermore, the strong correlation between inhibition of kinase activity and IL-1 and TNF-stimulated biological responses indicates that selective inhibition of the p38 MAPK pathway may have therapeutic utility in joint diseases such as rheumatoid arthritis (RA).
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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/Calcium Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0021-9541
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2001 Wiley-Liss, Inc.
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| pubmed:issnType |
Print
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| pubmed:volume |
187
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
294-303
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:11319753-Animals,
pubmed-meshheading:11319753-Biological Assay,
pubmed-meshheading:11319753-Bone Resorption,
pubmed-meshheading:11319753-Calcium Radioisotopes,
pubmed-meshheading:11319753-Cattle,
pubmed-meshheading:11319753-Cells, Cultured,
pubmed-meshheading:11319753-Chondrocytes,
pubmed-meshheading:11319753-Culture Techniques,
pubmed-meshheading:11319753-Cytokines,
pubmed-meshheading:11319753-Dose-Response Relationship, Drug,
pubmed-meshheading:11319753-Enzyme Activation,
pubmed-meshheading:11319753-Enzyme Inhibitors,
pubmed-meshheading:11319753-Growth Substances,
pubmed-meshheading:11319753-Humans,
pubmed-meshheading:11319753-Interleukin-1,
pubmed-meshheading:11319753-Interleukin-6,
pubmed-meshheading:11319753-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11319753-Osteoblasts,
pubmed-meshheading:11319753-Radius,
pubmed-meshheading:11319753-Rats,
pubmed-meshheading:11319753-Rats, Sprague-Dawley,
pubmed-meshheading:11319753-Signal Transduction,
pubmed-meshheading:11319753-Tumor Necrosis Factor-alpha,
pubmed-meshheading:11319753-Ulna,
pubmed-meshheading:11319753-p38 Mitogen-Activated Protein Kinases
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| pubmed:year |
2001
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| pubmed:articleTitle |
IL-1- and TNF-induced bone resorption is mediated by p38 mitogen activated protein kinase.
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| pubmed:affiliation |
Department of Musculoskeletal Diseases, Glaxo SmithKline, King of Prussia, Pennsylvania, USA. Sanjay_Kumar@SBPHRD.COM
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| pubmed:publicationType |
Journal Article
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