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Inhibition of NF-kappaB renders human juvenile costal chondrocyte cell lines sensitive to TNF-alpha-mediated cell death

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dc.contributor.authorYoon, H. S.-
dc.contributor.authorKim, H. A.-
dc.contributor.authorSong, Y. W.-
dc.date.accessioned2009-12-24T09:58:10Z-
dc.date.available2009-12-24T09:58:10Z-
dc.date.issued2005-02-11-
dc.identifier.citationRheumatol Int. 2006 Jan;26(3):201-8. Epub 2005 Feb 10.en
dc.identifier.issn0172-8172 (Print)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15703956-
dc.identifier.urihttps://hdl.handle.net/10371/22551-
dc.description.abstractBACKGROUND: Recently, therapeutics employing knowledge on various signaling pathways are being developed, with NF-kappaB being one of the most promising targets. NF-kappaB has been suggested to play a role not only in the induction of inflammatory mediators, but also in the protection from cell death. OBJECTIVES: This study pursued the role of the NF-kappaB pathway in the regulation of chondrocyte death induced by tumor necrosis factor alpha (TNF-alpha) and of the pertinent target molecules involved. METHODS: The human chondrocyte cell line C28/I2 was used for the experiment. Chondrocytes were transduced with adenovirus-encoding IkappaB (IkappaB) superrepressor which inhibits NF-kappaB activation, and treated with TNF-alpha. The proportion of cell death was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazdium bromide (MTT) assay. Activation of p38 mitogen activated protein (MAP) kinase and phosphatidylinositol 3-kinase (PI3K) by TNF-alpha was inhibited with SB202190 and Ly 294002 respectively. The expression of apoptosis related protein was analyzed with western blot assay, and the activation of c-Jun N-terminal kinase (JNK) by solid-phase kinase assay. RESULTS: Treatment with TNF-alpha led to cell death in 23% and 50% of ad-IkappaB-SR infected chondrocytes after 24 and 72 h respectively. The expression of Bcl-XL, Bcl-2, and XIAP significantly decreased, and activation of JNK was prolonged for up to 6 h in infected cells treated with TNF-alpha. Preincubation with p38 inhibitor or PI3K inhibitor before TNF-alpha led to a significant increase in cell death in ad-IkappaB-SR transduced chondrocytes, resulting in 53% and 30% cell death after 24 h for p38 inhibitor and PI3K inhibitor respectively. CONCLUSION: In our experimental system, specific inhibition of NF-kappaB activation rendered chondrocytes susceptible to cell death induced by TNF-alpha. The cell death was enhanced by inhibition of another signaling pathway such as p38 MAP kinase or PI3K. The expression of Bcl-XL, Bcl-2 and XIAP and activation of JNK were affected by ad-IkappaB-SR transduction, implying a role in the NF-kappaB regulated cell survival signaling in human chondrocytes.en
dc.language.isoen-
dc.publisherSpringer Verlagen
dc.subject1-Phosphatidylinositol 3-Kinase/antagonists & inhibitors/metabolismen
dc.subjectAdenoviridaeen
dc.subject*Apoptosis/drug effects/physiologyen
dc.subjectCell Lineen
dc.subjectChondrocytes/*drug effects/metabolism/virologyen
dc.subjectChromones/pharmacologyen
dc.subjectEnzyme Activationen
dc.subjectEnzyme Inhibitors/pharmacologyen
dc.subjectHumansen
dc.subjectImidazoles/pharmacologyen
dc.subjectJNK Mitogen-Activated Protein Kinases/metabolismen
dc.subjectMorpholines/pharmacologyen
dc.subjectNF-kappa B/*antagonists & inhibitors/metabolismen
dc.subjectPyridines/pharmacologyen
dc.subjectTransduction, Geneticen
dc.subjectTumor Necrosis Factor-alpha/*pharmacologyen
dc.subjectp38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolismen
dc.titleInhibition of NF-kappaB renders human juvenile costal chondrocyte cell lines sensitive to TNF-alpha-mediated cell deathen
dc.typeArticleen
dc.contributor.AlternativeAuthor윤호성-
dc.contributor.AlternativeAuthor김현아-
dc.contributor.AlternativeAuthor송영욱-
dc.identifier.doi10.1007/s00296-004-0562-x-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Immunology (면역학전공)Journal Papers (저널논문_면역학전공)
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