Neutrophil chemoattractant 2 beta regulates expression of the Reg gene in injured gastric mucosa in rats

Background & Aims: Regenerating (Reg) protein has a trophic effect on gastr ic mucosal cells. We have shown that Reg gene expression is increased in en terochromaffin-like (ECL) cells during the healing of damaged gastric mucos a around mucosal erosion. This study was designed to explore the stimulants of Reg expression during the healing of gastric mucosal damage. Methods: T ime course changes of the expression of genes for various proinflammatory c ytokines and Reg were investigated after induction of gastric mucosal lesio ns in rats. The direct effect of proinflammatory cytokines on Reg gene expr ession and Reg protein production were investigated in vitro using counterf low elutriation-enriched rat ECL cells. CXC receptor 2 (CXCR-2) expression was investigated in ECL cells by reverse-transcription polymerase chain rea ction. Reg gene expression was also investigated in rats treated by the neu tralizing antibody of cytokine-induced neutrophil chemoattractant (CINC-2 b eta). Results: During healing, the gene expression of several proinflammato ry cytokines and Reg was markedly augmented. Among the proinflammatory cyto kines, CINC-2 beta is the only cytokine in which augmented expression prece ded the increase of Reg gene expression. In rats treated with CINC-2 beta n eutralizing antibody, the augmentation of Reg gene expression was significa ntly inhibited. When ECL cells were incubated with these proinflammatory cy tokines, CINC-2 beta dose-dependently increased Reg messenger RNA and Reg p rotein in ECL cells. CXCR-2 was identified in isolated ECL cells. Conclusio ns: CINC-2 beta, expressed in damaged gastric mucosa, stimulates the produc tion of Reg protein in ECL cells via CXCR-2 and may be involved in the acce lerated healing of injured gastric mucosa.