Opposite effects of substance P and calcitonin gene-related peptide in oxazolone colitis.

Abstract

BACKGROUND:

Extrinsic sensory neurons play a crucial role in aberrant immune responses in colitis. The activation of peptidergic sensory nerve fibres is accompanied by a release of the neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP). SP levels increase whilst CGRP levels decrease in colon specimens from patients with inflammatory bowel disease; thus suggesting the pro- and anti-inflammatory roles, respectively, of these neuropeptides.

METHODS:

Oxazolone (4-ethoxymethylene-2-phenyl-2-oxazolin-5-one) colitis was induced in wild-type (WT), SP and CGRP knockout ((-/-)) mice. CGRP(-/-) mice were treated with the neurokinin 1-receptor antagonist CP-96345 (CP). The permeability of the mouse colon was evaluated by Evans Blue uptake. Cytokines produced by colonic lamina propria mononuclear cells were measured by ELISA.

RESULTS:

Colons of WT, CGRP(-/-) and SP(-/-) mice showed similar tissue architecture and permeability. SP(-/-) mice were protected against oxazolone colitis, whereas CGRP(-/-) showed increased susceptibility to colitis compared to WT mice. SP(-/-) and CP-treated CGRP(-/-) mice showed no significant body weight loss during the period of sickness in contrast to untreated CGRP(-/-) and WT mice. Decreased production of IL-4, IL-5, and IL-13 by colonic lamina propria mononuclear cells of the protected SP(-/-) mice confirms the crucial role of these cytokines in oxazolone colitis.

CONCLUSION:

We demonstrate that the neuropeptides CGRP and SP exert opposing effects in oxazolone colitis and provide further evidence for a prominent neuroimmune association in the gut.

• Authors: Matthias A Engel, Mohammad Khalil, Norbert Siklosi, Sonja M Mueller-Tribbensee, Winfried L Neuhuber, Markus F Neurath, Christoph Becker, Peter W Reeh
• Journal: Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver (Dig Liver Dis) Vol. 44 Issue 1 Pg. 24-9 (Jan 2012) ISSN: 1878-3562 [Electronic] Netherlands
• PMID: 22018693 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Cytokines
• Oxazolone
• Substance P
• Calcitonin Gene-Related Peptide

Topics

• Animals
• Calcitonin Gene-Related Peptide (genetics, metabolism)
• Colitis (chemically induced, metabolism)
• Colon (metabolism, pathology)
• Cytokines (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Inflammatory Bowel Diseases (metabolism, physiopathology)
• Mice
• Mice, Knockout
• Oxazolone
• Substance P (genetics, metabolism)