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

Abstract

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 E2 (PGE2)), decreased the secretion of proinflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6), inhibited the activation of c-Jun amino-terminal kinase (JNK), p38 and nuclear factor-κB (NF-κB) 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.

Practical Application of Urinary Zearalenone Monitoring System for Feed Hygiene Management of a Japanese Black Cattle Breeding Herd—The Relationship between Monthly Anti-Müllerian Hormone and Serum Amyloid A Concentrations

“…ZEN has been reported to have immunotoxicity in addition to its endocrine disrupting effects [31,32]. Previous reports indicated that ZEN exposure altered the hepatic cellular immune response, and suppressed the secretion of proinflammatory cytokines, such as IL-1, IL-6, and TNF-α [31][32][33]. Therefore, the negative regression trend between urinary ZEN and SAA concentrations obtained in the present study is possibly due to innate immune suppression of cows by low-level chronic ZEN exposure.…”

Modulatory Properties of Food and Nutraceutical Components Targeting NLRP3 Inflammasome Activation

“…Finally, food consumed as such, or after cooking processes, as well as water, may also contain internal or accidental components with a stimulating effect on NLRP3 inflammasome. Among these, mycotoxins (zearalenone, patulin, deoxynivalenol), trace metals (arsenic, cadmium), environmental and food contaminants (acrolein, 3-monochloropropane-1,2-diol, glycidol, and its esters), and acrylamide are few examples of NLRP3 activators, endowed with harmful inflammatory effects [ 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 ].…”

Staphylococcal Enterotoxin A Induces Intestinal Barrier Dysfunction and Activates NLRP3 Inflammasome via NF-κB/MAPK Signaling Pathways in Mice

“…The NLRP3 inflammasome is a vital part of the innate immune system and is composed of NLRP3, caspase-1 and apoptosis-associated speck-like protein containing CARD (ASC). Following recognition of PAMPs or DAMPs, the activation of NLRP3 inflammasome induces the maturation and release of proinflammatory cytokines, thereby triggering the progression of intestinal inflammation [19,20]. It is well known that the activation of NLRP3 inflammasome is often regulated by multiple intracellular signaling pathways, including nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) complexes [21].…”