Protease-activated receptor 1 suppresses Helicobacter pylori gastritis via the inhibition of macrophage cytokine secretion and interferon regulatory factor 5
Y-T Chionh, GZ Ng, L Ong, A Arulmuruganar, A Stent, MA Saeed, JLK Wee, P Sutton
MUCOSAL IMMUNOLOGY | NATURE PUBLISHING GROUP | Published : 2015
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..View full abstract
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Awarded by National Health and Medical Research Council of Australia
This work was supported by the Victorian Government's Operational Infrastructure Support Program and by Project grant 508963 from the National Health and Medical Research Council of Australia. P.S. is supported by a Senior Research Fellowship from the NHMRC. We gratefully acknowledge the assistance of Matthew Burton with flow cytometric analyses.