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Alpha-lipoic acid inhibits TNF-alpha induced NF-kappa B activation through blocking of MEKK1-MKK4-IKK signaling cascades
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Chang-Keun | - |
dc.contributor.author | Lee, Eun Young | - |
dc.contributor.author | Kim, Yong Gil | - |
dc.contributor.author | Mun, Se Hwan | - |
dc.contributor.author | Moon, Hee-Bom | - |
dc.contributor.author | Yoo, Bin | - |
dc.date.accessioned | 2010-01-29 | - |
dc.date.available | 2010-01-29 | - |
dc.date.issued | 2008-01-10 | - |
dc.identifier.citation | Int Immunopharmacol. 2008 Feb;8(2):362-70. Epub 2007 Nov 29. | en |
dc.identifier.issn | 1567-5769 (Print) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18182252 | - |
dc.identifier.uri | http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6W7N-4R7M8YS-1-F&_cdi=6631&_user=168665&_orig=search&_coverDate=02%2F29%2F2008&_sk=999919997&view=c&wchp=dGLbVzW-zSkWz&md5=d85d0ebaadec367e83848231e65d8ef5&ie=/sdarticle.pdf | - |
dc.identifier.uri | https://hdl.handle.net/10371/46572 | - |
dc.description.abstract | The therapeutic effects of alpha-lipoic acid (alpha-LA) via NF-kappa B down regulation were demonstrated on joint inflammation and erosion in an animal model. In this study, we investigated how alpha-LA inhibits the pathway of NF-kappa B activation by TNF-alpha via the mitogen-activated protein kinase (MAPK) pathway in rheumatoid arthritis (RA) fibroblast-like synovial cells (FLS). FLS were stimulated with TNF-alpha following pre-treatment with or without alpha-LA. Electrophoretic mobility shift assays (EMSA) revealed that TNF-alpha activates NF-kappa B in FLS. This was inhibited by alpha-LA at concentrations of 1 mM. TNF-alpha induced IKK mediated phosphorylation of GST-I kappa B and pre-treatment with alpha-LA inhibited this pathway. FLS constitutively express MEKK1, MEKK2, MEKK3, and TAK1 and that their levels are unaffected by TNF-alpha or alpha-LA. Immunoprecipitation using anti-MEKK1 antibody phosphorylated GST-I kappa B and pre-treating the cells with alpha-LA could abolish the reaction. FLS were immunoprecipitated using an antibody to MEKK1, and MKK4 was coprecipitated with MEKK1. In addition, immune complexes precipitated with anti-MKK4 antibody phosphorylated GST-I kappa B, and pre-treatment with alpha-LA inhibited the phosphorylation. Immunoprecipitation assay showed that MEKK1, MKK4, IKK-alpha, IKK-beta, I kappa B, and NF-kappa B comprised immunocomplex. It can be concluded that TNF-alpha activates NF-kappa B in FLS through MEKK1-MKK4-IKK signaling complex, and alpha-LA inhibits this signaling at the level of or upstream of IKK-alpha and IKK-beta. | en |
dc.language.iso | en | en |
dc.publisher | Elsevier | en |
dc.subject | Cells, Cultured | en |
dc.subject | Humans | en |
dc.subject | I-kappa B Kinase/*antagonists & inhibitors | en |
dc.subject | MAP Kinase Kinase 4/*antagonists & inhibitors | en |
dc.subject | MAP Kinase Kinase Kinase 1/*antagonists & inhibitors | en |
dc.subject | NF-kappa B/*metabolism | en |
dc.subject | Signal Transduction/*drug effects | en |
dc.subject | Thioctic Acid/*pharmacology | en |
dc.subject | Tumor Necrosis Factor-alpha/*antagonists & inhibitors | en |
dc.title | Alpha-lipoic acid inhibits TNF-alpha induced NF-kappa B activation through blocking of MEKK1-MKK4-IKK signaling cascades | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 이창근 | - |
dc.contributor.AlternativeAuthor | 이은영 | - |
dc.contributor.AlternativeAuthor | 김용길 | - |
dc.contributor.AlternativeAuthor | 문세환 | - |
dc.contributor.AlternativeAuthor | 문희봄 | - |
dc.contributor.AlternativeAuthor | 유빈 | - |
dc.identifier.doi | 10.1016/j.intimp.2007.10.020 | - |
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