RRC ID |
39967
|
著者 |
Hiraoka S, Miyazaki Y, Kitamura S, Toyota M, Kiyohara T, Shinomura Y, Mukaida N, Matsuzawa Y.
|
タイトル |
Gastrin induces CXC chemokine expression in gastric epithelial cells through activation of NF-kappaB.
|
ジャーナル |
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.
|
巻・号 |
281(3)
|
ページ |
G735-42
|
公開日 |
2001-9-1
|
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 |
3.725
|
引用数 |
31
|
WOS 分野
|
GASTROENTEROLOGY & HEPATOLOGY
PHYSIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
RGM1(RCB0876) |