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.

• Authors: Xavier Mas-Orea, Morgane Sebert, Mehdi Benamar, Camille Petitfils, Catherine Blanpied, Abdelhadi Saoudi, Céline Deraison, Frederick Barreau, Nicolas Cenac, Gilles Dietrich
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 14 (Jul 09 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34299013 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Anti-Inflammatory Agents, Non-Steroidal
• Cytokines
• IL10 protein, mouse
• Narcotic Antagonists
• Quaternary Ammonium Compounds
• Receptors, Opioid
• Interleukin-10
• Piroxicam
• Naloxone
• N-methylnaloxone

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Apoptosis (drug effects, genetics)
• CD4-Positive T-Lymphocytes (drug effects)
• Colitis (chemically induced, genetics, metabolism, pathology)
• Cytokines (genetics, metabolism)
• Epithelial Cells (drug effects)
• Inflammation (genetics, metabolism, pathology)
• Interleukin-10 (genetics, metabolism)
• Intestinal Mucosa (drug effects, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Naloxone (analogs & derivatives, pharmacology)
• Narcotic Antagonists (administration & dosage)
• Permeability (drug effects)
• Piroxicam (pharmacology)
• Quaternary Ammonium Compounds (pharmacology)
• Receptors, Opioid (metabolism)
• Severity of Illness Index