Zearalenone induces NLRP3-dependent pyroptosis via activation of NF-κB modulated by autophagy in INS-1 cells

Abstract

Zearalenone (ZEA), one of the mycotoxins widely found in food and feed, can stimulate an inflammatory reaction. In the present study, we demonstrated that ZEA induced the activation of NLRP3 inflammasome even pyroptotic cell death in rat Insulinoma Cell Line (INS-1). Meanwhile, according to the results of western blot and TEM, the level of autophagy was elevated by ZEA, which protected against the activation of NLRP3 inflammasome and inflammatory response caused by ZEA. Furthermore, we indicated that ZEA-induced NF-κB p65 activation contributed to the activation of the NLRP3 inflammasome, inflammatory response, and pyroptosis in INS-1 cells, which were indicated by western blot and immunofluorescence, and the activation of NF-κB p65 induced by ZEA was autophagy-dependent. This study demonstrates that ZEA induces NLRP3-dependent pyroptosis via activation of NF-κB modulated by autophagy in INS-1 cells.

Keywords: Autophagy; NF-κB p65; NLRP3 inflammasome; Pyroptosis; Zearalenone.