Gastrin induces CXC chemokine expression in gastric epithelial cells through activation of NF-kappa B

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.