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Inhibition of NF-kappaB renders human juvenile costal chondrocyte cell lines sensitive to TNF-alpha-mediated cell death
DC Field | Value | Language |
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dc.contributor.author | Yoon, H. S. | - |
dc.contributor.author | Kim, H. A. | - |
dc.contributor.author | Song, Y. W. | - |
dc.date.accessioned | 2009-12-24T09:58:10Z | - |
dc.date.available | 2009-12-24T09:58:10Z | - |
dc.date.issued | 2005-02-11 | - |
dc.identifier.citation | Rheumatol Int. 2006 Jan;26(3):201-8. Epub 2005 Feb 10. | en |
dc.identifier.issn | 0172-8172 (Print) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15703956 | - |
dc.identifier.uri | https://hdl.handle.net/10371/22551 | - |
dc.description.abstract | BACKGROUND: 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.iso | en | - |
dc.publisher | Springer Verlag | en |
dc.subject | 1-Phosphatidylinositol 3-Kinase/antagonists & inhibitors/metabolism | en |
dc.subject | Adenoviridae | en |
dc.subject | Cell Line | en |
dc.subject | Chondrocytes/*drug effects/metabolism/virology | en |
dc.subject | Chromones/pharmacology | en |
dc.subject | Enzyme Activation | en |
dc.subject | Enzyme Inhibitors/pharmacology | en |
dc.subject | Humans | en |
dc.subject | Imidazoles/pharmacology | en |
dc.subject | JNK Mitogen-Activated Protein Kinases/metabolism | en |
dc.subject | Morpholines/pharmacology | en |
dc.subject | NF-kappa B/*antagonists & inhibitors/metabolism | en |
dc.subject | Pyridines/pharmacology | en |
dc.subject | Transduction, Genetic | en |
dc.subject | Tumor Necrosis Factor-alpha/*pharmacology | en |
dc.subject | p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism | en |
dc.subject | Apoptosis/drug effects/physiology | - |
dc.title | Inhibition of NF-kappaB renders human juvenile costal chondrocyte cell lines sensitive to TNF-alpha-mediated cell death | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 윤호성 | - |
dc.contributor.AlternativeAuthor | 김현아 | - |
dc.contributor.AlternativeAuthor | 송영욱 | - |
dc.identifier.doi | 10.1007/s00296-004-0562-x | - |
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