Abstract
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 (p < 0.05). In IPEC-J2 cells, DON decreased cell viability and inhibited the expression of pBD1, pBD3, pEP2C, PG1-5, and PR39 (p < 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.
Highlights
Deoxynivalenol (DON) is one of the most prevalent trichothecene mycotoxin generated fromFusarium species and is commonly detected in cereals, such as wheat, corn, oats, rye and barley, all over the world [1]
No significant difference was observed among control, 1.28 mg/kg DON group, and 2.89 mg/kg DON group with regard to gain: feed (G:F)
To further explore the molecular mechanisms modulating the expression of Host defense peptides (HDPs) in IPEC-J2 cells, we investigated the possible involvement of key regulators that are responsible for the HDPs production
Summary
Deoxynivalenol (DON) is one of the most prevalent trichothecene mycotoxin generated from. Fusarium species and is commonly detected in cereals, such as wheat, corn, oats, rye and barley, all over the world [1]. Swine exhibit the highest sensitivity to DON. Consumption of diets contaminated with DON at ≥0.9 mg/kg causes anorexia, nutrient malabsorption, reduced weight gain, and immunologic alterations in pigs, especially for piglets [2]. Following ingestion of contaminated food or feed, DON is mainly absorbed in the intestine. The intestinal tract is the primary target for DON. Recent work has demonstrated that noncytotoxic concentration of DON
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