An OmpA-like protein from Acinetobacter spp. stimulates gastrin and interleukin-8 promoters

Bacterial overgrowth in the stomach may occur under conditions of diminishe d or absent acid secretion, Under these conditions, secretion of the hormon e gastrin is elevated. Alternatively, bacterial factors may directly stimul ate gastrin. Consistent with this hypothesis, we found that mice colonized for 2 months with a mixed bacterial culture of opportunistic pathogens show ed an increase in serum gastrin. To examine regulation of gene expression b y bacterial proteins, stable transformants of AGS cells expressing gastrin or interleukin-8 (IL-8) promoters were cocultured with live organisms. Both whole-cell sonicates and a heat-stable fraction were also coincubated with the cells. A level of 10(8) organisms per mi stimulated both the gastrin a nd IL-8 promoters. Heat-stable proteins prepared from these bacterial sonic ates stimulated the promoter significantly more than the live organism or u nheated sonicates. A 38-kDa heat-stable protein stimulating the gastrin and IL-8 promoters was cloned and found to be an OmpA-related protein. Immunob lotting using antibody to the OmpA-like protein identified an Acinetobacter sp. as the bacterial species that expressed this protein and colonized the mouse stomach. Moreover, reintubation of mice with a pure culture of the A cinetobacter sp. caused gastritis. We conclude that bacterial colonization of the stomach may increase serum gastrin levels in part through the abilit y of the bacteria to produce OmpA-like proteins that directly stimulate gas trin and IL-8 gene expression. These results implicate OmpA-secreting bacte ria in the activation of gastrin gene expression and raise the possibility that a variety of organisms may contribute to the increase in serum gastrin and subsequent epithelial cell proliferation in the hypochlorhydric stomac h.