Mycotoxin Zearalenone Attenuates Innate Immune Responses and Suppresses NLRP3 Inflammasome Activation in LPS-Activated Macrophages

Zearalenone (ZEA) is a mycotoxin that has several adverse effects on most mammalian species. However, the effects of ZEA on macrophage-mediated innate immunity during infection have not been examined. In the present study, bacterial lipopolysaccharides (LPS) were used to induce the activation of macrophages and evaluate the effects of ZEA on the inflammatory responses and inflammation-associated signaling pathways. The experimental results indicated that ZEA suppressed LPS-activated inflammatory responses by macrophages including attenuating the production of proinflammatory mediators (nitric oxide (NO) and prostaglandin E-2 (PGE(2))), decreased the secretion of proinflammatory cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6), inhibited the activation of c-Jun amino-terminal kinase (JNK), p38 and nuclear factor-kappa B (NF-kappa B) signaling pathways, and repressed the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. These results indicated that mycotoxin ZEA attenuates macrophage-mediated innate immunity upon LPS stimulation, suggesting that the intake of mycotoxin ZEA-contaminated food might result in decreasing innate immunity, which has a higher risk of adverse effects during infection.

Automated summary

ZEA suppresses macrophage-mediated innate immunity activated by LPS, attenuating the production of proinflammatory mediators and cytokines, inhibiting inflammatory signaling pathways, and repressing inflammasome activation. This suggests that ZEA-contaminated food intake may decrease innate immunity and increase adverse effects during infection.