Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism

Cathy Nguyen (1) , Anne-Marie Coelho (1) , Eileen Grady (1) , Steven J Compton (1) , John L Wallace (1) , Morley D Hollenberg (1) , Nicolas Cenac (1) , Rafael Garcia Villar (2) , Lionel Bueno (1) , Martin Steinhoff (1) , Nigel W Bunnett (1) , Nathalie Vergnolle (1)

1 Chercheur indépendant
2 ToxAlim - ToxAlim

Proteinase-activated receptor-2 (PAR2) activation induces colonic inflammation by an unknown mechanism. We hypothesized that PAR2 agonists administered intracolonically in mice induce inflammation via a neurogenic mechanism. Pretreatment of mice with neurokinin-1 and calcitonin-gene-related peptide (CGRP) receptor antagonists or with capsaicin showed attenuated PAR2-agonist-induced colitis. Immunohistochemistry demonstrated a differential expression of a marker for the type-1 CGRP receptor during the time course of PAR2-agonist-induced colitis, further suggesting a role for CGRP. We conclude that PAR2-agonist-induced intestinal inflammation involves the release of neuropeptides, which by acting on their receptors cause inflammation. These results implicate PAR2 as an important mediator of intestinal neurogenic inflammation.

Domaines: Sciences du Vivant [q-bio]

Cathy Nguyen, Anne-Marie Coelho, Eileen Grady, Steven J Compton, John L Wallace, et al.. Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism. Canadian Journal of Physiology and Pharmacology, 2003, 81 (9), pp.920-927. ⟨hal-01562306⟩