5,7-dihydroxy-3,4,6-trimethoxyflavone inhibits the inflammatory effects induced byBacteroides fragilisenterotoxin via dissociating the complex of heat shock protein 90 and IκBα and IκB kinase-γ in intestinal epithelial cell culture
Open Access
- 19 November 2008
- journal article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 155 (3), 541-551
- https://doi.org/10.1111/j.1365-2249.2008.03849.x
Abstract
Enterotoxin produced by enterotoxigenic Bacteroides fragilis (BFT) has been associated with mucosal inflammation and diarrhoeal diseases. In this study, the anti-inflammatory molecular mechanism of 5,7-dihydroxy-3,4,6-trimethoxyflavone (eupatilin) was characterized in an HT-29 intestinal epithelial cell line stimulated with BFT. Pre-treatment of HT-29 cells with eupatilin decreased the production significantly of both interleukin (IL)-8 and prostaglandin E2 induced by BFT in a dose-dependent manner. BFT-activated nuclear factor-kappaB (NF-κB) signals in HT-29 cells and pretreatment with eupatilin suppressed NF-κB activation that resulted in the significant inhibition of IL-8 and cyclo-oxygenase-2 expression. BFT-induced phosphorylation of both IκBα and IκB kinase (IKK) signals was prevented in eupatilin-pretreated HT-29 cells. Transfection of siRNA for IKK-α and IKK-β decreased the production of IL-8 and prostaglandin E2; however, the transfection of IKK-β siRNA showed a more significant reduction of BFT-induced IκBα phosphorylation compared with that of IKK-α siRNA. In addition, herbimycin A, a specific inhibitor of heat shock protein 90 (Hsp90), decreased the BFT-induced activation of IKK and NF-κB, suggesting that Hsp90 is associated with a pathway of IKK-NF-κB-IL-8/cyclo-oxygenase-2 gene signalling. Furthermore, eupatilin dissociated the complex between Hsp90 and IKK-γ in BFT-stimulated HT-29 cells. These results suggest that eupatilin can suppress the NF-κB signalling pathway by targeting the Hsp90-IKK-γ complex in intestinal epithelial cells and may attenuate BFT-induced inflammatory responses.Keywords
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