The anti-inflammatory agents aspirin and salicylate inhibit the activity of IκB kinase-β

Min-Jean Yin, Yumi Yamamoto and Richard B. Gaynor ()
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Min-Jean Yin: Harold Simmons Cancer Center, University of Texas Southwestern Medical Center
Yumi Yamamoto: Harold Simmons Cancer Center, University of Texas Southwestern Medical Center
Richard B. Gaynor: Harold Simmons Cancer Center, University of Texas Southwestern Medical Center

Nature, 1998, vol. 396, issue 6706, 77-80

Abstract: Abstract 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 response1,2. 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 nucleus3,4,5,6,7,8,9. IKK kinase activity is stimulated when cells are exposed to the cytokine TNF-α or by overexpression of the cellular kinases MEKK1 and NIK10,11. 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.

Date: 1998
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DOI: 10.1038/23948

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