| pubmed-article:9973483 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:9973483 | lifeskim:mentions | umls-concept:C0521447 | lld:lifeskim |
| pubmed-article:9973483 | lifeskim:mentions | umls-concept:C0021081 | lld:lifeskim |
| pubmed-article:9973483 | lifeskim:mentions | umls-concept:C0063041 | lld:lifeskim |
| pubmed-article:9973483 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:9973483 | lifeskim:mentions | umls-concept:C0870883 | lld:lifeskim |
| pubmed-article:9973483 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:9973483 | lifeskim:mentions | umls-concept:C1533157 | lld:lifeskim |
| pubmed-article:9973483 | lifeskim:mentions | umls-concept:C0100724 | lld:lifeskim |
| pubmed-article:9973483 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:9973483 | pubmed:dateCreated | 1999-4-13 | lld:pubmed |
| pubmed-article:9973483 | pubmed:abstractText | Leflunomide is a novel immunosuppressive and antiinflammatory agent currently being tested for treatment of autoimmune diseases and transplant rejection. NF-kappa B is a transcription factor activated in response to a wide variety of inflammatory stimuli, including TNF, but whether leflunomide blocks NF-kappa B activation is not known. In the present report we demonstrate that treatment of a human T cell line (Jurkat) with leflunomide blocks TNF-mediated NF-kappa B activation in a dose- and time-dependent manner, with maximum inhibition at 5-10 microM. Inhibition was not restricted to TNF-induced activation, because leflunomide also inhibited NF-kappa B activation induced by other inflammatory agents, including phorbol ester, LPS, H2O2, okadaic acid, and ceramide. Leflunomide blocked the degradation of I kappa B alpha and subsequent nuclear translocation of the p65 subunit, steps essential for NF-kappa B activation. This correlated with inhibition of dual specificity-mitogen-activated protein kinase kinase as well as an Src protein tyrosine kinase, p56lck, by leflunomide. Reducing agents did not reverse the effect of leflunomide. Leflunomide also suppressed the TNF-activated NF-kappa B-dependent reporter gene expression. Our results thus indicate that leflunomide is a potent inhibitor of NF-kappa B activation induced by a wide variety of inflammatory stimuli, and this provides the molecular basis for its anti-inflammatory and immunosuppressive effects. | lld:pubmed |
| pubmed-article:9973483 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:9973483 | pubmed:citationSubset | AIM | lld:pubmed |
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| pubmed-article:9973483 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:9973483 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:9973483 | pubmed:issn | 0022-1767 | lld:pubmed |
| pubmed-article:9973483 | pubmed:author | pubmed-author:AggarwalB BBB | lld:pubmed |
| pubmed-article:9973483 | pubmed:author | pubmed-author:MannaS KSK | lld:pubmed |
| pubmed-article:9973483 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:9973483 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:9973483 | pubmed:volume | 162 | lld:pubmed |
| pubmed-article:9973483 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:9973483 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:9973483 | pubmed:pagination | 2095-102 | lld:pubmed |
| pubmed-article:9973483 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:9973483 | pubmed:year | 1999 | lld:pubmed |
| pubmed-article:9973483 | pubmed:articleTitle | Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression. | lld:pubmed |
| pubmed-article:9973483 | pubmed:affiliation | Cytokine Research Laboratory, Department of Molecular Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. | lld:pubmed |
| pubmed-article:9973483 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:9973483 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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