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Inhibition of Vasoactive Intestinal Polypeptide (VIP) Induces Resistance to Dextran Sodium Sulfate (DSS)-Induced Colitis in Mice

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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 μM) or PG 97–269 (1 nM) had significantly reduced clinical signs of colitis. Furthermore, colonic expression of IL-1ϐ, TNF-α, 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.

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Grant Support

Department of Veterans Affairs Merit Review (PG, JP) NIH DK-41301 & RO1 DK-078676 (MM)

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Authors and Affiliations

  1. CURE/Digestive Diseases Research Center, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles and VA Greater Los Angeles Health Care System, Los Angeles, CA, USA

    John P. Vu, Mulugeta Million, Muriel Larauche, Leon Luong, Joshua Norris, James A. Waschek, Charalabos Pothoulakis, Joseph R. Pisegna & Patrizia M. Germano

  2. Department of Psychiatry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    James A. Waschek

  3. Division of Pulmonary and Critical Care, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA

    Patrizia M. Germano

  4. Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Charalabos Pothoulakis

  5. Division of Gastroenterology and Hepatology, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA

    Joseph R. Pisegna

  6. CURE/UCLA West Los Angeles VA Healthcare System, Bldg. 115 Rm 313, Los Angeles, CA, USA

    Patrizia M. Germano

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  1. John P. Vu
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Correspondence to Patrizia M. Germano.

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Vu, J.P., Million, M., Larauche, M. et al. Inhibition of Vasoactive Intestinal Polypeptide (VIP) Induces Resistance to Dextran Sodium Sulfate (DSS)-Induced Colitis in Mice. J Mol Neurosci 52, 37–47 (2014). https://doi.org/10.1007/s12031-013-0205-3

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