关键词: IPEC-J2 Nrf2 allicin intestinal barrier lipopolysaccharide oxidative damage

Mesh : Animals Cell Line Disulfides / pharmacology Electric Impedance Endoplasmic Reticulum Stress / drug effects Epithelial Cells / metabolism Heme Oxygenase-1 / metabolism Jejunum / drug effects metabolism physiology Lipopolysaccharides / toxicity NF-E2-Related Factor 2 / metabolism Permeability / drug effects Signal Transduction / drug effects Sulfinic Acids / pharmacology Swine Tight Junction Proteins / metabolism

来  源:   DOI:10.3389/fimmu.2022.847861   PDF(Pubmed)

Abstract:
Gut barrier disruption is the initial pathogenesis of various diseases. We previously reported that dietary allicin improves tight junction proteins in the endoplasmic reticulum stressed jejunum. However, whether the allicin benefits the gut barrier within mycotoxin or endotoxin exposure is unknown. In the present study, IPEC-J2 cell monolayers within or without deoxynivalenol (DON) or lipopolysaccharide (LPS) challenges were employed to investigate the effects of allicin on intestinal barrier function and explore the potential mechanisms. Results clarified that allicin at 2 μg/mL increased the viability, whereas the allicin higher than 10 μg/mL lowered the viability of IPEC-J2 cells via inhibiting cell proliferation. Besides, allicin increased trans-epithelial electric resistance (TEER), decreased paracellular permeability, and enhanced ZO-1 integrity of the IPEC-J2 cell monolayers. Finally, allicin supplementation prevented the LPS-induced barrier damages via activating Nrf2/HO-1 pathway-dependent antioxidant system. In conclusion, the present study strongly confirmed allicin as an effective nutrient to improve intestinal barrier function and prevent bacterial endotoxin-induced barrier damages.
摘要:
肠道屏障破坏是各种疾病的初始发病机制。我们先前报道,饮食大蒜素可改善内质网应激空肠中的紧密连接蛋白。然而,大蒜素是否有益于真菌毒素或内毒素暴露中的肠道屏障尚不清楚.在本研究中,采用或不采用脱氧雪腐镰刀菌烯醇(DON)或脂多糖(LPS)攻击的IPEC-J2细胞单层来研究大蒜素对肠屏障功能的影响并探索潜在的机制。结果阐明,大蒜素在2μg/mL时增加了活力,而高于10μg/mL的大蒜素通过抑制细胞增殖降低了IPEC-J2细胞的活力。此外,大蒜素增加跨上皮电阻(TEER),细胞旁通透性降低,和增强的IPEC-J2细胞单层的ZO-1完整性。最后,大蒜素补充通过激活Nrf2/HO-1途径依赖性抗氧化系统来预防LPS诱导的屏障损伤。总之,本研究强烈证实大蒜素是改善肠屏障功能和防止细菌内毒素引起的屏障损伤的有效营养素。
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