IRSD, Université de Toulouse-Paul Sabatier, INSERM, INRAe, ENVT, UPS, 31000 Toulouse, France.
INFINITY, Université de Toulouse-Paul Sabatier, INSERM, CNRS, UPS, 31000 Toulouse, France.
Int J Mol Sci. 2021 Jul 9;22(14):7387. doi: 10.3390/ijms22147387.
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.
黏膜 CD4 T 淋巴细胞在白细胞介素 (IL)-10 敲除的炎症性肠病 (IBD) 小鼠模型中表现出强大的阿片介导的镇痛活性。考虑到内源性阿片类物质在外周也可能表现出抗炎活性，我们通过纳洛酮-甲碘化物（一种不能通过血脑屏障的通用阿片受体拮抗剂）检查了外周阿片受体阻断对白细胞介素-10 缺陷（IL-10）小鼠吡罗昔康加速结肠炎发展的影响。在这里，我们表明，用吡罗昔康治疗的 IL-10 缺陷型小鼠表现出肠道屏障功能的显著改变，包括通透性、炎症相关生物活性脂质介质和黏膜 CD4 T 淋巴细胞亚群。在外周阻断阿片受体几乎对结肠炎的严重程度没有影响，但显著加重了上皮细胞凋亡和肠道通透性。因此，尽管内源性阿片类物质的张力不足以显著减轻结肠炎的严重程度，但它对保护上皮屏障的物理完整性有很大的贡献。
