위상피세포주에서 타우린 포합 담즙산에 의한 Nuclear Factor - Kappa B 매개 Interleukin - 8 의 발현

Abstract

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- B) on the expression of IL-8. Methods: After the gastric epithelial cells were treated with TC or TCDC, time courses of NF- B binding activity and IL-8 secretion were determined by electrophoretic mobility shift assay (EMSA) and ELISA. To evaluate the role of NF- B on the expression of IL-8, IL-8 levels were assessed after pretreatment with rebamipide or pyrrolidine dithiocarbamate (PDTC), known as NF- B inhibitors, or phosphorothioate-modified anti-sense (AS) oligonucleotides (ODN) for p50 subunit of NF- B. 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- B binding complex within 60 min. Pre-incubation of the cells with PDTC (100 M), rebamipide (0.1 and 0.5 mM) or AS-ODN caused significant decreases in IL-8 secretion induced by TC or TCDC. Conclusions: NF- B 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.