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

Aiping Zhao, Motoko Morimoto, Harry Dawson, Justin E. Elfrey, Kathleen B. Madden, William C. Gause, Booki Min, Fred D. Finkelman, Joseph F. Urban, Terez Shea-Donohue*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2563-2569
Number of pages7
JournalJournal of Immunology
Volume175
Issue number4
DOIs
StatePublished - Aug 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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