Dataset Information

Peripheral Opioid Receptor Blockade Enhances Epithelial Damage in Piroxicam-Accelerated Colitis in IL-10-Deficient Mice.

ABSTRACT: Mucosal CD4+ T lymphocytes display a potent opioid-mediated analgesic activity in interleukin (IL)-10 knockout mouse model of inflammatory bowel diseases (IBD). Considering that endogenous opioids may also exhibit anti-inflammatory activities in the periphery, we examined the consequences of a peripheral opioid receptor blockade by naloxone-methiodide, a general opioid receptor antagonist unable to cross the blood-brain barrier, on the development of piroxicam-accelerated colitis in IL-10-deficient (IL-10-/-) mice. Here, we show that IL-10-deficient mice treated with piroxicam exhibited significant alterations of the intestinal barrier function, including permeability, inflammation-related bioactive lipid mediators, and mucosal CD4+ T lymphocyte subsets. Opioid receptor antagonization in the periphery had virtually no effect on colitis severity but significantly worsened epithelial cell apoptosis and intestinal permeability. Thus, although the endogenous opioid tone is not sufficient to reduce the severity of colitis significantly, it substantially contributes to the protection of the physical integrity of the epithelial barrier.

SUBMITTER: Mas-Orea X

PROVIDER: S-EPMC8304158 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

Peripheral Opioid Receptor Blockade Enhances Epithelial Damage in Piroxicam-Accelerated Colitis in IL-10-Deficient Mice.

Mas-Orea Xavier X Sebert Morgane M Benamar Mehdi M Petitfils Camille C Blanpied Catherine C Saoudi Abdelhadi A Deraison Céline C Barreau Frederick F Cenac Nicolas N Dietrich Gilles G

International journal of molecular sciences 20210709 14

Mucosal CD4<sup>+</sup> T lymphocytes display a potent opioid-mediated analgesic activity in interleukin (IL)-10 knockout mouse model of inflammatory bowel diseases (IBD). Considering that endogenous opioids may also exhibit anti-inflammatory activities in the periphery, we examined the consequences of a peripheral opioid receptor blockade by naloxone-methiodide, a general opioid receptor antagonist unable to cross the blood-brain barrier, on the development of piroxicam-accelerated colitis in I ...[more]

PMID: 34299013

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Project description:BackgroundA multitude of mouse models are utilized to emulate and study intestinal inflammation. T-cell receptor alpha chain (TCRα)-deficient mice are used as a model of spontaneous colitis that has similarities with human ulcerative colitis. However, colitis is triggered late in the life of the mouse (age: 4-5 months), and inflammation does not develop at the same time in different mice. A previously conducted study reported that the administration of the drug piroxicam triggered predictable and early colitis in TCRα-deficient mice at the age of 6-8 weeks. However, a detailed characterization of ensuing inflammation was not provided.MethodsWe conducted an in-depth examination of piroxicam-triggered colitis in TCRα-deficient mice, with emphasis on spatial histopathologic changes and analysis of expression of inflammatory markers. Furthermore, we tested amelioration of colitis with dexamethasone.ResultsWe confirmed that piroxicam induced a time-prescribed colitis and did so in the proximal colon as well as the cecum of TCRα-deficient mice. Piroxicam administration was observed to induce epithelial hyperplasia, goblet cell loss, and leukocyte infiltration with occasional ulceration. A Swiss roll technique was used to examine the colon and cecum in its entirety. Importantly, we observed that inflammation was multifocal segmental, with areas of tissue damage in between healthy tissue. In addition, we observed variability in the severity of inflammation among replicate animals and treatments, and that the administration of dexamethasone only partially ameliorated inflammation in the proximal colon.ConclusionsPiroxicam consistently induced multifocal segmental colitis in the proximal colon and cecum, although the degree of inflammation was reduced in the latter. Importantly, spatial variability in inflammation in the large intestine and the inter-replicate variation in the severity of inflammation must be taken into consideration when utilizing this murine model of synchronized colitis.

Dataset Information

Peripheral Opioid Receptor Blockade Enhances Epithelial Damage in Piroxicam-Accelerated Colitis in IL-10-Deficient Mice.

Publications

Peripheral Opioid Receptor Blockade Enhances Epithelial Damage in Piroxicam-Accelerated Colitis in IL-10-Deficient Mice.

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