RGD Reference Report - Opposite effects of substance P and calcitonin gene-related peptide in oxazolone colitis. - Rat Genome Database

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

Authors: Engel, MA  Khalil, M  Siklosi, N  Mueller-Tribbensee, SM  Neuhuber, WL  Neurath, MF  Becker, C  Reeh, PW 
Citation: Engel MA, etal., Dig Liver Dis. 2012 Jan;44(1):24-9. Epub 2011 Oct 22.
RGD ID: 5687148
Pubmed: PMID:22018693   (View Abstract at PubMed)
DOI: DOI:10.1016/j.dld.2011.08.030   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colitis  ISOIl5 (Mus musculus)5687148; 5687148protein: increased expressionRGD 
colitis  IEP 5687148protein: increased expressionRGD 
inflammatory bowel disease susceptibilityISOIl5 (Mus musculus)5687148; 5687148 RGD 
inflammatory bowel disease susceptibilityIEP 5687148 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il5  (interleukin 5)

Genes (Mus musculus)
Il5  (interleukin 5)

Genes (Homo sapiens)
IL5  (interleukin 5)


Additional Information