RRC ID 39967
Author Hiraoka S, Miyazaki Y, Kitamura S, Toyota M, Kiyohara T, Shinomura Y, Mukaida N, Matsuzawa Y.
Title Gastrin induces CXC chemokine expression in gastric epithelial cells through activation of NF-kappaB.
Journal Am. J. Physiol. Gastrointest. Liver Physiol.
Abstract Although hypergastrinemia is frequently observed in individuals with a chronic Helicobacter pylori infection, its pathophysiological significance in gastric mucosal inflammation is unclear. The present study was designed to determine if gastrin induces the expression of CXC chemokines in gastric epithelial cells. Human and rat gastric epithelial cells, transfected with gastrin receptor, were stimulated with gastrin. The expression of mRNAs for human interleukin-8 (IL-8) and rat cytokine-induced neutrophil chemoattractant-1 and release of human IL-8 protein were then determined by Northern blot analysis and ELISA, respectively. Gastrin not only induced the expression of mRNAs for these chemokines but also stimulated IL-8 protein release. A luciferase assay using IL-8 promoter genes showed that nuclear factor (NF)-kappaB is absolutely required and activator protein-1 (AP-1) is partly required for the maximum induction of IL-8 by gastrin. An electrophoretic mobility shift assay revealed that gastrin is capable of activating both NF-kappaB and AP-1. In addition, the inhibition of NF-kappaB abrogated gastrin-induced chemokine expression. These results suggest that gastrin is capable of upregulating CXC chemokines in gastric epithelial cells and therefore may contribute to the progression of the inflammatory process in the stomach.
Volume 281(3)
Pages G735-42
Published 2001-9
DOI 10.1152/ajpgi.2001.281.3.G735
PMID 11518686
MeSH Animals Cell Line Chemokine CXCL1 Chemokines, CXC / biosynthesis* Chemokines, CXC / genetics Chemotactic Factors / biosynthesis Chemotactic Factors / genetics Dose-Response Relationship, Drug Epithelial Cells / cytology Epithelial Cells / drug effects Epithelial Cells / metabolism* Gastric Mucosa / cytology Gastric Mucosa / drug effects Gastric Mucosa / metabolism* Gastrins / pharmacology* Gene Expression / drug effects Gene Expression Regulation / drug effects Growth Substances / biosynthesis Growth Substances / genetics Humans Intercellular Signaling Peptides and Proteins* Interleukin-1 / pharmacology Interleukin-8 / biosynthesis Interleukin-8 / genetics NF-kappa B / antagonists & inhibitors NF-kappa B / metabolism* Promoter Regions, Genetic / genetics Pyrrolidines / pharmacology RNA, Messenger / metabolism Rats Receptors, Cholecystokinin / genetics Receptors, Cholecystokinin / metabolism Thiocarbamates / pharmacology Transcription Factor AP-1 / metabolism Transfection Tumor Necrosis Factor-alpha / pharmacology
IF 3.729
Times Cited 29
Human and Animal Cells