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 I kappa B alpha and I kappa B kinase-gamma in intestinal epithelial cell culture
- Authors
- Kim, Jung Mogg; Lee, Dong Ho; Kim, Joo Sung; Lee, Jin-Young; Park, Hwon Gyeom; Kim, Yeoung-Jeon; Oh, Yu Kyoung; Jung, Hyun Chae; Kim, Sa Il
- Issue Date
- Mar-2009
- Publisher
- OXFORD UNIV PRESS
- Keywords
- Bacteroides fragilis enterotoxin; eupatilin; Hsp90; I kappa B kinase; NF-kappa B
- Citation
- CLINICAL AND EXPERIMENTAL IMMUNOLOGY, v.155, no.3, pp.541 - 551
- Indexed
- SCIE
SCOPUS
- Journal Title
- CLINICAL AND EXPERIMENTAL IMMUNOLOGY
- Volume
- 155
- Number
- 3
- Start Page
- 541
- End Page
- 551
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/177179
- DOI
- 10.1111/j.1365-2249.2008.03849.x
- ISSN
- 0009-9104
- 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 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.
- Files in This Item
-
Go to Link
- Appears in
Collections - 서울 의과대학 > 서울 미생물학교실 > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.