Proteinase-activated receptor-2-induced colonic inflammation in mice: Possible involvement of afferent neurons, nitric oxide, and paracellular permeability

Nicolas Cenac, Rafael Garcia-Villar, Laurent Ferrier, Muriel Larauche, Nathalie Vergnolle, Nigel W. Bunnett, Anne Marie Coelho, Jean Fioramonti, Lionel Bueno

Research output: Contribution to journalArticle

Abstract

Activation of colonic proteinase-activated receptor-2 (PAR-2) provokes colonic inflammation and increases mucosal permeability in mice. The mechanism of inflammation is under debate and could be neurogenic and/or the consequence of tight-junction opening with passage of exogenous pathogens into the lamina propria. The present study aimed to further characterize the inflammatory effect of PAR-2 activation by investigating: 1) the role of NO, 2) the role of afferent neurons, and 3) a possible cause and effect relationship between colonic paracellular permeability changes and mucosal inflammation. Thus, intracolonic infusion to mice of the PAR-2-activating peptide, SLIGRL, increased both myeloperoxidase (MPO) activity and damage scores indicating colonic inflammation, and enhanced colonic permeability to 51Cr-EDTA from 2 to 4 h after its infusion. NO synthase inhibitors, L-NAME and aminoguanidine, as well as the neurotoxin capsaicin and NK1, calcitonin gene-related peptide (CGRP) receptor antagonists, SR140333 and CGRP8-37, prevented SLIGRL-induced MPO and damage score increases and permeability. In contrast, although the tight-junction blocker, 2,4,6-triaminopyrimidine, and the myosin L chain kinase inhibitor, ML-7, prevented SLIGRL-induced increase in permeability, they did not prevent MPO and damage score increases. Taken together our data show that both NO and capsaicin-sensitive afferent neurons are involved in PAR-2-mediated colonic inflammation and paracellular permeability increase. Nevertheless, the inflammation process is not a consequence of increased permeability which results at least in part from the activation of myosin L chain kinase.

Original languageEnglish (US)
Pages (from-to)4296-4300
Number of pages5
JournalJournal of Immunology
Volume170
Issue number8
DOIs
StatePublished - Apr 15 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Cenac, N., Garcia-Villar, R., Ferrier, L., Larauche, M., Vergnolle, N., Bunnett, N. W., Coelho, A. M., Fioramonti, J., & Bueno, L. (2003). Proteinase-activated receptor-2-induced colonic inflammation in mice: Possible involvement of afferent neurons, nitric oxide, and paracellular permeability. Journal of Immunology, 170(8), 4296-4300. https://doi.org/10.4049/jimmunol.170.8.4296