Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
Toxins (Basel). 2018 Dec 15;10(12):541. doi: 10.3390/toxins10120541.
Host defense peptides (HDPs) are efficient defense components of the innate immune system, playing critical roles in intestinal homeostasis and protection against pathogens. This study aims to investigate the interference effects of DON on the intestinal porcine HDPs expression in piglets and intestinal porcine epithelial cell line (IPEC-J2) cells, and elucidate the underlying mechanisms through which it functions. In an animal experiment, intestinal HDPs were determined in weaned piglets fed control and 1.28 mg/kg or 2.89 mg/kg DON-contaminated diets. Dietary exposure to DON significantly decreased piglet average daily gain, increased intestinal permeability and depressed the expression of porcine β-defensin1 (pBD1), pBD2, pBD3, epididymis protein 2 splicing variant C (pEP2C), PMAP23, and proline/arginine-rich peptide of 39 amino acids (PR39) in the intestine ( < 0.05). In IPEC-J2 cells, DON decreased cell viability and inhibited the expression of pBD1, pBD3, pEP2C, PG1-5, and PR39 ( < 0.05). NOD2, key regulator that is responsible for HDPs production, was markedly downregulated, whereas caspase-12 was activated in the presence of DON. In conclusion, DON induced caspase-12 activation and inhibited the NOD2-mediated HDPs production, which led to an impaired intestinal barrier integrity of weaned piglets. Our study provides a promising target for future therapeutic strategies to prevent the adverse effects of DON.
宿主防御肽(HDPs)是先天免疫系统的有效防御成分,在肠道稳态和抵御病原体方面发挥着关键作用。本研究旨在探讨 DON 对仔猪肠道猪 HDPs 表达的干扰作用及其作用机制。在动物实验中,用对照和 1.28mg/kg 或 2.89mg/kg DON 污染日粮喂养断奶仔猪,检测肠道 HDPs。日粮中 DON 的暴露显著降低了仔猪的平均日增重,增加了肠道通透性,并降低了肠道中猪 β-防御素 1(pBD1)、pBD2、pBD3、附睾蛋白 2 拼接变体 C(pEP2C)、PMAP23 和富含脯氨酸/精氨酸的 39 个氨基酸肽(PR39)的表达(<0.05)。在 IPEC-J2 细胞中,DON 降低了细胞活力并抑制了 pBD1、pBD3、pEP2C、PG1-5 和 PR39 的表达(<0.05)。DON 存在时,NOD2(负责 HDPs 产生的关键调节因子)明显下调,而 caspase-12 被激活。综上所述,DON 诱导 caspase-12 激活并抑制 NOD2 介导的 HDPs 产生,导致断奶仔猪肠道屏障完整性受损。我们的研究为未来预防 DON 不良影响的治疗策略提供了一个有前途的靶点。