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Cell Immunol. 2011;267(2):124-32. doi: 10.1016/j.cellimm.2011.01.001. Epub 2011 Jan 7.

VPAC1 (vasoactive intestinal peptide (VIP) receptor type 1) G protein-coupled receptor mediation of VIP enhancement of murine experimental colitis.

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1
Department of Medicine, University of California Medical Center, San Francisco, CA 94143, USA. mahesh.yadav@ucsf.edu

Abstract

Distinct roles of the two T cell G protein-coupled receptors for vasoactive intestinal peptide (VIP), termed VPAC1 and VPAC2, in VIP regulation of autoimmune diseases were investigated in the dextran sodium sulfate (DSS)-induced murine acute colitis model for human inflammatory bowel diseases. In mice lacking VPAC2 (VPAC2-KO), DSS-induced colitis appeared more rapidly with greater weight loss and severe histopathology than in wild-type mice. In contrast, DSS-induced colitis in VPAC1-KO mice was milder than in wild-type mice and VPAC2-KO mice. Tissues affected by colitis showed significantly higher levels of myeloperoxidase, IL-6, IL-1β and MMP-9 in VPAC2-KO mice than wild-type mice, but there were no differences for IL-17, IFN-γ, IL-4, or CCR6. Suppression of VPAC1 signals in VPAC2-KO mice by PKA inhibitors reduced the clinical and histological severity of DSS-induced colitis, as well as tissue levels of IL-6, IL-1β and MMP-9. Thus VIP enhancement of the severity of DSS-induced colitis is mediated solely by VPAC1 receptors.

PMID:
21295288
DOI:
10.1016/j.cellimm.2011.01.001
[Indexed for MEDLINE]

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