Proteinase-Activated Receptor-2-Induced Colonic Inflammation in Mice: Possible Involvement of Afferent Neurons, Nitric Oxide, and Paracellular Permeability
Open accessAbstract
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.
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- Authors
- Cenac, N., Garcia-Villar, R., Ferrier, L., Larauche, M., Vergnolle, N., Bunnett, N. W., Coelho, A.-M., Fioramonti, J., & Bueno, L.
- Affiliations
- Neuro-Gastroenterology and Nutrition Unit, Institut National de la Recherche Agronomique , Toulouse ,
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- University of Calgary (CA)
- University of California, San Francisco (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-04
- Volume
- 170
- Issue
- 8
- Pages
- 4296-4300
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1534629774
- Cited by
- 139
- References
- 32
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 2 · 2014: 5 · 2013: 3 · 2012: 3
- FWCI
- 9.48
- Type
- journal article
- Language
- en
- Open access
- green
- hal.inrae.fr
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- protease-activated receptor 2, colonic inflammation, nitric oxide, sensory neurons, capsaicin-sensitive neurons, paracellular permeability, mucosal permeability, tight junctions, calcitonin gene-related peptide, neurokinin-1 receptor, myeloperoxidase, neurogenic inflammation, 2,4,6-triaminopyrimidine
- MeSH terms
- Calcitonin Gene-Related Peptide Receptor Antagonists, Administration, Rectal, Animals, Antigens, Antigens, Surface, Azepines, Cell Membrane Permeability, Colon, Denervation, Enzyme Inhibitors, Inflammation, Injections, Intraperitoneal, Intercellular Junctions, Intestinal Mucosa, Male, Myosin-Light-Chain Kinase, Naphthalenes, Neurons, Afferent, Nitric Oxide, Oligopeptides, Peptide Fragments, Piperidines, Proteins, Pyrimidines, Quinuclidines, Calcitonin Gene-Related Peptide, Receptors, Thrombin, Nitric Oxide Synthase, Lectins, C-Type, Receptor, PAR-2, Mice, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, NK Cell Lectin-Like Receptor Subfamily B
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