Master Program in Food Safety, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan.
Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
Toxicology. 2021 Mar 30;452:152698. doi: 10.1016/j.tox.2021.152698. Epub 2021 Jan 29.
Hyperglycemia induces low-grade systemic inflammation and immune dysregulation, leading to overstated reactions to immune stimuli and diabetes-related organ damage. Tissue inflammation is characterized by leukocyte infiltration, and T cells play crucial roles in directing leukocyte-mediated inflammatory responses. The aim of the study was to investigate the effects of dietary exposure to chlorpyrifos (CPF) on systemic and hepatic immune-cell phenotypes in C57BL/6 mice with streptozotocin (STZ)-induced diabetes. Mice received an intraperitoneal injection of STZ for 5 consecutive days to induce diabetes, and diabetic mice were given either an AIN-93-based control diet or a CPF-containing diet at doses of 0.5, 1, or 2 mg/kg body weight/day for 28 days. Results showed that dietary exposure to CPF had no influence on the body weight or the erythrocyte hemoglobin A1c level in diabetic mice. Both blood and hepatic neutrophil populations were enhanced by CPF exposure. CPF-exposed groups had lower percentages of blood T cells without altering the proportions of CD4 and CD8 T-cell subsets, and lower expression levels of the Bcl-2 antiapoptotic gene in the spleen. CPF exposure reduced the percentage of blood regulatory T cells (Tregs); however, the Treg population was upregulated in the liver even when hepatic T cells were not affected by CPF in diabetic mice. Hepatic expressions of Treg-related genes were suppressed in all CPF-exposed groups. Higher plasma levels of aspartate aminotransferase and expression levels of the hepatic interleukin-1β gene were observed in diabetic mice exposed to medium and high doses of CPF. These findings suggest that dietary exposure to CPF affects the distribution of both myeloid and lymphoid immune cells in the blood and liver under hyperglycemic conditions, which may lead to hyperinflammation when encountering immune stimuli.
高血糖会引起低度全身炎症和免疫失调，导致对免疫刺激物的反应过度和与糖尿病相关的器官损伤。组织炎症的特征是白细胞浸润，T 细胞在指导白细胞介导的炎症反应中起着至关重要的作用。本研究旨在研究膳食接触毒死蜱（CPF）对链脲佐菌素（STZ）诱导糖尿病 C57BL/6 小鼠全身和肝脏免疫细胞表型的影响。小鼠连续 5 天腹腔注射 STZ 诱导糖尿病，糖尿病小鼠给予基于 AIN-93 的对照饮食或含 CPF 的饮食，剂量为 0.5、1 或 2mg/kg 体重/天，持续 28 天。结果表明，膳食接触 CPF 对糖尿病小鼠的体重或红细胞血红蛋白 A1c 水平没有影响。CPF 暴露均增强了血液和肝脏中性粒细胞群体。CPF 暴露组的血液 T 细胞比例降低，但 CD4 和 CD8 T 细胞亚群的比例不变，脾脏中 Bcl-2 抗凋亡基因的表达水平降低。CPF 暴露降低了血液调节性 T 细胞（Tregs）的比例；然而，即使在糖尿病小鼠中肝 T 细胞不受 CPF 影响的情况下，CPF 暴露也会使肝脏中的 Treg 群体上调。CPF 暴露组的肝 Treg 相关基因表达均受到抑制。在接触中、高剂量 CPF 的糖尿病小鼠中，血浆天冬氨酸转氨酶水平升高，肝脏白细胞介素-1β 基因的表达水平升高。这些发现表明，在高血糖条件下，膳食接触 CPF 会影响血液和肝脏中髓样和淋巴样免疫细胞的分布，当遇到免疫刺激物时，可能导致过度炎症。
