Master Program in Food Safety, College of Nutrition, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 11031, Taiwan.
Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
Arch Toxicol. 2020 Jan;94(1):141-150. doi: 10.1007/s00204-019-02615-2. Epub 2019 Dec 5.
Inflammatory bowel disease (IBD) is associated with loss of immune tolerance to antigens originating from the diet and from the gut microflora. T cells play crucial roles in the pathogenesis of IBD. Chlorpyrifos (CPF) is one of the most ubiquitous organophosphate pesticides in the world. The aim of the study was to investigate the effects of dietary exposure to CPF on T-cell populations in C57BL/6 mice with dextran sulfate sodium (DSS)-induced colitis. Mice received distilled water containing 3% DSS for 6 days to induce acute colitis, which was then replaced with distilled water for 21 days, allowing progression to chronic inflammation. During the experimental period, mice were given either an AIN-93-based control diet or a CPF diet-containing 7, 17.5, or 35 ppm of CPF. Results showed that dietary exposure to CPF significantly increased circulating neutrophils in colitic mice. CPF-exposed groups had lower percentages of blood and spleen T cells without altering the proportions of CD4 and CD8 T-cell subsets. The percentage of blood regulatory T (Treg) cells, as well as splenic expressions of Treg-related genes, were suppressed in CPF-exposed mice. CPF upregulated the colonic gene expression of tumor necrosis factor-α. Meanwhile, plasma haptoglobin, colon weights, and luminal immunoglobulin G levels were higher in CPF-exposed groups. Histopathological analyses also observed that colon injury was more severe in all CPF-exposed mice. These results suggest that dietary exposure to CPF aggravated tissue injuries in mice with DSS-induced chronic colitis by suppressing T-cell populations and Treg polarization.
炎症性肠病 (IBD) 与对源自饮食和肠道微生物群的抗原的免疫耐受丧失有关。T 细胞在 IBD 的发病机制中起关键作用。毒死蜱 (CPF) 是世界上最普遍的有机磷农药之一。本研究旨在研究饮食暴露于 CPF 对葡聚糖硫酸钠 (DSS) 诱导的结肠炎 C57BL/6 小鼠 T 细胞群体的影响。小鼠接受含 3% DSS 的蒸馏水 6 天以诱导急性结肠炎，然后用蒸馏水替代 21 天，允许进展为慢性炎症。在实验期间，小鼠给予基于 AIN-93 的对照饮食或含有 7、17.5 或 35 ppm CPF 的 CPF 饮食。结果表明，饮食暴露于 CPF 可显著增加结肠炎小鼠循环中的中性粒细胞。CPF 暴露组的血液和脾脏 T 细胞百分比降低，而 CD4 和 CD8 T 细胞亚群的比例没有改变。CPF 暴露组的血液调节性 T (Treg) 细胞百分比以及脾脏 Treg 相关基因的表达受到抑制。CPF 上调了结肠肿瘤坏死因子-α的基因表达。同时，CPF 暴露组的血浆触珠蛋白、结肠重量和腔免疫球蛋白 G 水平升高。组织病理学分析还观察到所有 CPF 暴露组的结肠损伤更严重。这些结果表明，饮食暴露于 CPF 通过抑制 T 细胞群体和 Treg 极化加重了 DSS 诱导的慢性结肠炎小鼠的组织损伤。
