The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta.

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阅读量：

263

作者：

MJ Yin，Y Yamamoto，RB Gaynor

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摘要：

NF-κB comprises a family of cellular transcription factors that are involved in the inducible expression of a variety of cellular genes that regulate the inflammatory response,. NF-κB is sequestered in the cytoplasm by inhibitory proteins, IκB, which are phosphorylated by a cellular kinase complex known as IKK. IKK is made up of two kinases, IKK-α and IKK-β, which phosphorylate IκB, leading to its degradation and translocation of NF-κB to the nucleus. IKK kinase activity is stimulated when cells are exposed to the cytokine TNF-α or by overexpression of the cellular kinases MEKK1 and NIK,. Here we demonstrate that the anti-inflammatory agents aspirin and sodium salicylate specifically inhibit IKK-β activity in vitro and in vivo. The mechanism of aspirin and sodium salicylate inhibition is due to binding of these agents to IKK-β to reduce ATP binding. Our results indicate that the anti-inflammatory properties of aspirin and salicylate are mediated in part by their specific inhibition of IKK-β, thereby preventing activation by NF-κB of genes involved in the pathogenesis of the inflammatory response.

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关键词：

rate-dependent plasticity self-consistent estimates heterogeneous materials creep of polycrystals second-order theory nonlinear homogenization

DOI：

10.1038/23948

被引量：

5015

年份：

1998