title: Gastrin induces CXC chemokine expression in gastric epithelial cells through activation of NF-kappaB.
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.
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 565-0871 Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hiraoka
authors.forename: Y
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: S
authors.initials: S
authors.lastname: Kitamura
authors.forename: M
authors.initials: M
authors.lastname: Toyota
authors.forename: T
authors.initials: T
authors.lastname: Kiyohara
authors.forename: Y
authors.initials: Y
authors.lastname: Shinomura
authors.forename: N
authors.initials: N
authors.lastname: Mukaida
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000818:Animals; D002460:Cell Line; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000235:genetics / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D005755:Gastrins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; D013859:Thiocarbamates; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid