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

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

doi:10.1139/y03-080

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

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

Molecular Pathobiology

Research output: Contribution to journal › Article › peer-review

Abstract

Proteinase-activated receptor-2 (PAR₂) activation induces colonic inflammation by an unknown mechanism. We hypothesized that PAR ₂ 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.

Original language	English (US)
Pages (from-to)	920-927
Number of pages	8
Journal	Canadian Journal of Physiology and Pharmacology
Volume	81
Issue number	9
DOIs	https://doi.org/10.1139/y03-080
State	Published - Sep 1 2003

Keywords

Calcitonin-gene-related peptide
Colitis
Neurogenic inflammation
Neurokinin-1 receptors
Proteinase-activated receptor-2
Substance P
Trypsin

ASJC Scopus subject areas

Physiology
Pharmacology
Physiology (medical)

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10.1139/y03-080

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Nguyen, C., Coelho, A. M., Grady, E., Compton, S. J., Wallace, J. L., Hollenberg, M. D., Cenac, N., Garcia-Villar, R., Bueno, L., Steinhoff, M., Bunnett, N. W., & Vergnolle, N. (2003). Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism. Canadian Journal of Physiology and Pharmacology, 81(9), 920-927. https://doi.org/10.1139/y03-080

Nguyen, C, Coelho, AM, Grady, E, Compton, SJ, Wallace, JL, Hollenberg, MD, Cenac, N, Garcia-Villar, R, Bueno, L, Steinhoff, M, Bunnett, NW & Vergnolle, N 2003, 'Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism', Canadian Journal of Physiology and Pharmacology, vol. 81, no. 9, pp. 920-927. https://doi.org/10.1139/y03-080

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title = "Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism",

abstract = "Proteinase-activated receptor-2 (PAR2) activation induces colonic inflammation by an unknown mechanism. We hypothesized that PAR 2 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.",

keywords = "Calcitonin-gene-related peptide, Colitis, Neurogenic inflammation, Neurokinin-1 receptors, Proteinase-activated receptor-2, Substance P, Trypsin",

author = "Cathy Nguyen and Coelho, {Anne Marie} and Eileen Grady and Compton, {Steven J.} and Wallace, {John L.} and Hollenberg, {Morley D.} and Nicolas Cenac and Rafael Garcia-Villar and Lionel Bueno and Martin Steinhoff and Bunnett, {Nigel W.} and Nathalie Vergnolle",

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AU - Coelho, Anne Marie

AU - Grady, Eileen

AU - Compton, Steven J.

AU - Wallace, John L.

AU - Hollenberg, Morley D.

AU - Cenac, Nicolas

AU - Garcia-Villar, Rafael

AU - Bueno, Lionel

AU - Steinhoff, Martin

AU - Bunnett, Nigel W.

AU - Vergnolle, Nathalie

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N2 - Proteinase-activated receptor-2 (PAR2) activation induces colonic inflammation by an unknown mechanism. We hypothesized that PAR 2 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.

AB - Proteinase-activated receptor-2 (PAR2) activation induces colonic inflammation by an unknown mechanism. We hypothesized that PAR 2 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.

KW - Calcitonin-gene-related peptide

KW - Colitis

KW - Neurogenic inflammation

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

Abstract

Keywords

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