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Publication : Immune regulation of protease-activated receptor-1 expression in murine small intestine during Nippostrongylus brasiliensis infection.

First Author  Zhao A Year  2005
Journal  J Immunol Volume  175
Issue  4 Pages  2563-9
PubMed ID  16081830 Mgi Jnum  J:107492
Mgi Id  MGI:3621322 Doi  10.4049/jimmunol.175.4.2563
Citation  Zhao A, et al. (2005) Immune regulation of protease-activated receptor-1 expression in murine small intestine during Nippostrongylus brasiliensis infection. J Immunol 175(4):2563-9
abstractText  Infection with gastrointestinal nematodes exerts profound effects on both immune and physiological responses of the host. Helminth infection induces a hypercontractility of intestinal smooth muscle that is dependent on the Th2 cytokines, IL-4 and IL-13, and may contribute to worm expulsion. Protease-activated receptors (PARs) are expressed throughout the gut, and activation of PAR-1 was observed in asthma, a Th2-driven pathology. In the current study we investigated the physiologic and immunologic regulation of PAR-1 in the murine small intestine, specifically 1) the effect of PAR-1 agonists on small intestinal smooth muscle contractility, 2) the effects of Nippostrongylus brasiliensis infection on PAR-1 responses, 3) the roles of IL-13 and IL-4 in N. brasiliensis infection-induced alterations in PAR-1 responses, and 4) the STAT6 dependence of these responses. We demonstrate that PAR-1 activation induces contraction of murine intestinal smooth muscle that is enhanced during helminth infection. This hypercontractility is associated with an elevated expression of PAR-1 mRNA and protein. N. brasiliensis-induced changes in PAR-1 function and expression were seen in IL-4-deficient mice, but not in IL-13- or STAT6-deficient mice, indicating the dependence of IL-13 on the STAT6 signaling pathway independent of IL-4.
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