S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
5,7-dihydroxy-3,4,6-trimethoxyflavone inhibits the inflammatory effects induced by Bacteroides fragilis enterotoxin via dissociating the complex of heat shock protein 90 and IκBα and IκB kinase-γ in intestinal epithelial cell culture
- Kim, J. M.; Lee, D. H.; Kim, J. S.; Lee, J. Y.; Kim, Y. -J.; Jung, H. C.; Kim, S. I.; Oh, Y. -K.; Park, H. -G.
- Issue Date
- CLINICAL AND EXPERIMENTAL IMMUNOLOGY; Vol.155 3; 541-551
- 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 E(2) induced by BFT in a dose-dependent manner. BFT-activated nuclear factor-kappaB (NF-kappa B) signals in HT-29 cells and pretreatment with eupatilin suppressed NF-kappa B activation that resulted in the significant inhibition of IL-8 and cyclo-oxygenase-2 expression. BFT-induced phosphorylation of both I kappa B alpha and I kappa B kinase (IKK) signals was prevented in eupatilin-pretreated HT-29 cells. Transfection of siRNA for IKK-alpha and IKK-beta decreased the production of IL-8 and prostaglandin E(2); however, the transfection of IKK-beta siRNA showed a more significant reduction of BFT-induced I kappa B alpha phosphorylation compared with that of IKK-alpha siRNA. In addition, herbimycin A, a specific inhibitor of heat shock protein 90 (Hsp90), decreased the BFT-induced activation of IKK and NF-kappa B, suggesting that Hsp90 is associated with a pathway of IKK-NF-kappa B-IL-8/cyclo-oxygenase-2 gene signalling. Furthermore, eupatilin dissociated the complex between Hsp90 and IKK-gamma in BFT-stimulated HT-29 cells. These results suggest that eupatilin can suppress the NF-kappa B signalling pathway by targeting the Hsp90-IKK-gamma complex in intestinal epithelial cells and may attenuate BFT-induced inflammatory responses.
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