S. Hiraoka et al., Gastrin induces CXC chemokine expression in gastric epithelial cells through activation of NF-kappa B, AM J P-GAST, 281(3), 2001, pp. G735-G742
Citations number
46
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Although hypergastrinemia is frequently observed in individuals with a chro
nic Helicobacter pylori infection, its pathophysiological significance in g
astric mucosal inflammation is unclear. The present study was designed to d
etermine if gastrin induces the expression of CXC chemokines in gastric epi
thelial cells. Human and rat gastric epithelial cells, transfected with gas
trin receptor, were stimulated with gastrin. The expression of mRNAs for hu
man interleukin-8 (IL-8) and rat cytokine-induced neutrophil chemoattractan
t-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 l
uciferase assay using IL-8 promoter genes showed that nuclear factor (NF)-k
appaB is absolutely required and activator protein-1 (AP-1) is partly requi
red for the maximum induction of IL-8 by gastrin. An electrophoretic mobili
ty shift assay revealed that gastrin is capable of activating both NF-kappa
B and AP-1. In addition, the inhibition of NF-kappaB abrogated gastrin-indu
ced chemokine expression. These results suggest that gastrin is capable of
upregulating CXC chemokines in gastric epithelial cells and therefore may c
ontribute to the progression of the inflammatory process in the stomach.