Protease-activated receptor 1 suppresses Helicobacter pylori gastritis via the inhibition of macrophage cytokine secretion and interferon regulatory factor 5

Abstract

Chronic gastritis from Helicobacter pylori infection is a major factor in the development of gastric adenocarcinoma. Factors that regulate gastritis severity are important in determining which individuals are susceptible to H. pylori-associated disease. Although protease-activated receptor 1 (PAR1) has been identified as one such host factor, its mechanism of action is unknown. Using chimeric mice, we demonstrated that PAR1-mediated protection against H. pylori gastritis requires bone marrow-derived cells. Analyses of the gastric mucosa revealed that PAR1 suppresses cellular infiltration and both T helper type 1 (Th1) and T helper type 17 (Th17) responses to infection. Moreover, PAR1 express..