Deoxynivalenol (DON), a trichothecene mycotoxin, exerts pro-inflammatory and immunomodulatory activity. Interleukin (IL)-1β serves a crucial part as a gate keeper of inflammation in DON-induced macrophages, but an overview of how DON exposure elicits IL-1β secretion from RAW264.7 cells has not been fully illustrated. Here we found that the cellular phenomenon, involved with a type of programmed cell death known as pyroptosis, contains: 1) increase of pro-IL-1β expression, 2) motivation of caspase-1, 3) caspase-1-dependent maturement of IL-1β, 4) caspase-1 fragmentation of gasdermin D (GSDMD), and 5) IL-1β secretion through GSDMD pore. Mechanistically, the present study certified that DON both as first and second signals engaged in IL-1β release is mediated by purinergic P2X7 receptor (P2X7R)-Src signaling. During this process, P2X7R signal is required for GSDMD pore forming course in ASC-independent manner. Moreover, blocking of K+ efflux, ROS formation, as well as cathepsin B activity decreases IL-1β export. Our data show that exposure to DON does cause pyroptosis and IL-1β secretion via P2X7R signal in RAW264.7 macrophages. Overall, these results provide new mechanistic clue for DON as a pro-inflammatory factor in innate immune signaling events.

Department of Chemistry Faculty of Science University of Hradec Kralove Hradec Kralove 50003 Czech Republic

MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary Medicine Nanjing Agricultural University Nanjing 210095 China

MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary Medicine Nanjing Agricultural University Nanjing 210095 China; MOE Engineering Research Center of Bio process School of Food and Biological Engineering Hefei University of Technology Hefei 230009 China

MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary Medicine Nanjing Agricultural University Nanjing 210095 China; MOE Engineering Research Center of Bio process School of Food and Biological Engineering Hefei University of Technology Hefei 230009 China; Department of Chemistry Faculty of Science University of Hradec Kralove Hradec Kralove 50003 Czech Republic

School of Biology and Food Engineering Changshu Institute of Technology Suzhou 215500 China

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