Korean J Gastroenterol.
2002 Mar;39(3):204-215.
Taurine-conjugated Bile Acids Induce Nuclear Factor-Kappa B Mediated Interleukin-8 Activation in Gastric Epithelial Cell Lines
- Affiliations
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- 1Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. gidept@wonju.yonsei.ac.kr
- 2Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
- 3Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Abstract
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BACKGROUND/AIMS: The molecular mechanism of gastric epithelial injury induced by bile acid remains poorly understood. The aims of this study were to examine whether IL-8 was expressed by the stimulation of human gastric epithelial cells (AGS and Kato III) with taurine-conjugated bile acids, taurocholic acid (TC) or taurochenodeoxycholic acid (TCDC), and to evaluate the role of Nuclear Factor-Kappa B (NF-kappaB) on the expression of IL-8.
METHODS
After the gastric epithelial cells were treated with TC or TCDC, time courses of NF-kappaB binding activity and IL-8 secretion were determined by electrophoretic mobility shift assay (EMSA) and ELISA. To evaluate the role of NF-kappaB on the expression of IL-8, IL-8 levels were assessed after pretreatment with rebamipide or pyrrolidine dithiocarbamate (PDTC), known as NF-kappaB inhibitors, or phosphorothioate-modified anti-sense (AS) oligonucleotides (ODN) for p50 subunit of NF-kappaB.
RESULTS
TC or TCDC stimulation increased IL-8 secretion in a time and dose-dependent manner. Moreover, AGS and Kato III cells treated with TC or TCDC dose-dependently induced a prominent NF-kappaB binding complex within 60 min. Pre-incubation of the cells with PDTC (100 nM), rebamipide (0.1 and 0.5 mM) or AS-ODN caused significant decreases in IL-8 secretion induced by TC or TCDC.
CONCLUSIONS
NF-kappaB mediated IL-8 expression may play an important role in the taurine-conjugated bile acid-induced gastric epithelial injury and may present a plausible molecular mechanism for the bile reflux gastritis.