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Inhibition of vasoactive intestinal polypeptide (VIP) induces resistance to dextran sodium sulfate (DSS)-induced colitis in mice.


ABSTRACT: VIP is highly expressed in the colon and regulates motility, vasodilatation, and sphincter relaxation. However, its role in the development and progress of colitis is still controversial. Our aim was to determine the participation of VIP on dextran sodium sulfate (DSS)-induced colonic mucosal inflammation using VIP(-/-) and WT mice treated with VIP antagonists. Colitis was induced in 32 adult VIP(-/-) and 14 age-matched WT litter-mates by giving 2.5 % DSS in the drinking water. DSS-treated WT mice were injected daily with VIP antagonists, VIPHyb (n?=?22), PG 97-269 (n?=?9), or vehicle (n?=?31). After euthanasia, colons were examined; colonic cytokines mRNA were quantified. VIP(-/-) mice were remarkably resistant to DSS-induced colitis compared to WT. Similarly, DSS-treated WT mice injected with VIPHyb (1 ?M) or PG 97-269 (1 nM) had significantly reduced clinical signs of colitis. Furthermore, colonic expression of IL-1?, TNF-?, and IL-6 was significantly lower in VIP(-/-) and VIPHyb or PG 97-269 compared to vehicle-treated WT. Genetic deletion of VIP or pharmacological inhibition of VIP receptors resulted in resistance to colitis. These data demonstrate a pro-inflammatory role for VIP in murine colitis and suggest that VIP antagonists may be an effective clinical treatment for human inflammatory bowel diseases.

SUBMITTER: Vu JP 

PROVIDER: S-EPMC4114158 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Inhibition of vasoactive intestinal polypeptide (VIP) induces resistance to dextran sodium sulfate (DSS)-induced colitis in mice.

Vu John P JP   Million Mulugeta M   Larauche Muriel M   Luong Leon L   Norris Joshua J   Waschek James A JA   Pothoulakis Charalabos C   Pisegna Joseph R JR   Germano Patrizia M PM  

Journal of molecular neuroscience : MN 20140107 1


VIP is highly expressed in the colon and regulates motility, vasodilatation, and sphincter relaxation. However, its role in the development and progress of colitis is still controversial. Our aim was to determine the participation of VIP on dextran sodium sulfate (DSS)-induced colonic mucosal inflammation using VIP(-/-) and WT mice treated with VIP antagonists. Colitis was induced in 32 adult VIP(-/-) and 14 age-matched WT litter-mates by giving 2.5 % DSS in the drinking water. DSS-treated WT mi  ...[more]

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