Somatostatin inhibits dendritic cell responsiveness to Helicobacter pylori

Abstract

Somatostatin is a regulatory peptide found in abundance in the stomach. We have previously shown that somatostatin is required for IL-4-mediated resolution of Helicobacter pylori gastritis. In the current study, we hypothesize that somatostatin acts directly on antigen-presenting cells in the stomach to lessen the severity of gastritis. To test this hypothesis, we first show that CD11c+ dendritic cells are present in the infected tissue of mice with H. pylori-induced gastritis. Pretreatment of bone marrow-derived dendritic cells with somatostatin results in decreased IL-12 production, and lower splenocyte proliferation induced by H. pylori-stimulated dendritic cells. Furthermore, octreotide, a somatostatin analogue, is more potent than somatostatin in suppressing IL-12 release by H. pylori-stimulated dendritic cells through an NF-kappaB-independent pathway. In addition, IL-4 stimulates somatostatin secretion from dendritic cells. In conclusion, somatostatin inhibits dendritic cell activation by H. pylori; a possible mechanism by which IL-4 mediates resolution of gastritis. We suggest that octreotide may be effective in treating immune-mediated diseases of the stomach.