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• W4384701191 endingPage "102946" @default.
• W4384701191 startingPage "102946" @default.
• W4384701191 abstract "Zearalenone (ZEA) is produced mainly by fungi belonging to the genus Fusarium in foods and feeds. Heterophil extracellular traps (HETs) are a novel defense of chicken innate immunity involving activated heterophils. However, the conditions and requirements for ZEA-triggered HET release remain unknown. In this study, immunostaining analysis demonstrated that the ZEA-triggered extracellular fibers were composed of histone and elastase assembled on the DNA skeleton, showing that ZEA can induce the formation of HETs. Further experiments indicated that ZEA-induced HET release was concentration-dependent, ranging from 20 to 80 μM ZEA, and time-dependent, ranging from 30 to 180 min. Moreover, in 80 μM ZEA-exposed chicken heterophils, reactive oxygen species (ROS) level, catalase (CAT), superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and glutathione (GSH) content were increased. Simultaneously, ZEA at 80 μM activated ERK and p38 MAPK signaling pathways by increasing the phosphorylation level of ERK and p38 proteins. The pharmacological inhibition assays revealed that the inhibition of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, ERK, and p38 mitogen-activated protein kinase (MAPK) lowered the ZEA-induced ROS significantly but did not influence HET formation. Furthermore, immunostaining analysis indicated that the heterophil underwent the formation of autophagosome based on being stained with LC3B. The pharmacological inhibition assays demonstrated that rapamycin-, wortmannin-, and 3-Methyladenine (3-MA)-treatments modulated ZEA-triggered HET formation, indicating that heterophil autophagy plays a key role in ZEA-induced HET formation. Further studies on energy metabolism showed that inhibition of lactate/glucose transport, hexokinase-2 (HK-2), fructose-2,6-biphosphatase 3 (PFKFB3) in glycolysis abated ZEA-induced HETs, implying that glycolysis is one of the factors influencing the ZEA-induced HET formation. Besides, inhibition of the peptidylarginine deiminase (PAD) enzyme and P2X1 significantly reduced the ZEA-induced HET formation. In conclusion, we demonstrated that ZEA triggered HET formation, which was associated with glycolysis, autophagy, PAD enzyme, and P2X1 receptor activation, providing valuable insight into the effect of ZEA on chicken innate immunity." @default.
• W4384701191 created "2023-07-20" @default.
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• W4384701191 date "2023-10-01" @default.
• W4384701191 modified "2023-10-16" @default.
• W4384701191 title "The release of zearalenone-induced heterophil extracellular traps in chickens is associated with autophagy, glycolysis, PAD enzyme, and P2X1 receptor" @default.
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• W4384701191 doi "https://doi.org/10.1016/j.psj.2023.102946" @default.
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