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Báo cáo y học: "α Does protein kinase R mediate TNF-α- and ceramide-induced increases in expression and activation of matrix metalloproteinases in articular cartilage by a novel mechanism"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: α Does protein kinase R mediate TNF-α- and ceramide-induced increases in expression and activation of matrix metalloproteinases in articular cartilage by a novel mechanism? | Arthritis Research Therapy Vol 6 No 1 Gilbert et al. Research article Open Access Does protein kinase R mediate TNF-a- and ceramide-induced increases in expression and activation of matrix metalloproteinases in articular cartilage by a novel mechanism Sophie J Gilbert Victor C Duance and Deborah J Mason Connective Tissue Biology Laboratories School of Biosciences Cardiff University Cardiff Wales UK Correspondence Sophie J Gilbert e-mail GilbertSJ1@Cardiff.ac.uk Received 24 Jul 2003 Revisions requested 15 Sep 2003 Revisions received 14 Oct 2003 Accepted 21 Oct 2003 Published 12 Nov 2003 Arthritis Res Ther 2004 6 R46-R55 DOI 10.1186 ar1024 2004 Gilbert et al. licensee BioMed Central Ltd Print ISSN 1478-6354 Online ISSN 1478-6362 . This is an Open Access article verbatim copying and redistribution of this article are permitted in all media for any purpose provided this notice is preserved along with the article s original URL. Abstract We investigated the role of the proinflammatory cytokine TNF-a the second messenger C2-ceramide and protein kinase R PKR in bovine articular cartilage degradation. Bovine articular cartilage explants were stimulated with C2-ceramide or TNF-a for 24 hours. To inhibit the activation of PKR 2-aminopurine was added to duplicate cultures. Matrix metalloproteinase MMP expression and activation in the medium were analysed by gelatin zymography proteoglycan release by the dimethylmethylene blue assay and cell viability by the Cytotox 96 assay. C2-ceramide treatment of cartilage explants resulted in a significant release of both pro- and active MMP-2 into the medium. Small increases were also seen with TNF-a treatment. Incubation of explants with 2-aminopurine before TNF-a or C2-ceramide treatment resulted in a marked reduction in expression and activation of both MMP-2 and MMP-9. TNF-a and C2-ceramide significantly increased proteoglycan release into the medium which was also inhibited by cotreatment with 2-aminopurine. A loss of cell viability