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
  • 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

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.

Keyword

Taurine-conjugated bile acids; NF-kappaB; Interleukin-8; Gastric epithelial cell lines

MeSH Terms

Bile Acids and Salts*
Bile Reflux
Bile*
Electrophoretic Mobility Shift Assay
Enzyme-Linked Immunosorbent Assay
Epithelial Cells*
Gastritis
Humans
Interleukin-8*
NF-kappa B
Oligonucleotides
Taurochenodeoxycholic Acid
Taurocholic Acid
Bile Acids and Salts
Interleukin-8
NF-kappa B
Oligonucleotides
Taurochenodeoxycholic Acid
Taurocholic Acid
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