Gossypol induces pyroptosis in mouse macrophages via a non-canonical inflammasome pathway

Toxicology and Applied Pharmacology
Qiu-Ru LinXian-Hui He

Abstract

Gossypol, a polyphenolic compound isolated from cottonseeds, has been reported to possess many pharmacological activities, but whether it can influence inflammasome activation remains unclear. In this study, we found that in mouse macrophages, gossypol induced cell death characterized by rapid membrane rupture and robust release of HMGB1 and pro-caspase-11 comparable to ATP treatment, suggesting an induction of pyroptotic cell death. Unlike ATP, gossypol induced much low levels of mature interleukin-1β (IL-1β) secretion from mouse peritoneal macrophages primed with LPS, although it caused pro-IL-1β release similar to that of ATP. Consistent with this, activated caspase-1 responsible for pro-IL-1β maturation was undetectable in gossypol-treated peritoneal macrophages. Besides, RAW 264.7 cells lacking ASC expression and caspase-1 activation also underwent pyroptotic cell death upon gossypol treatment. In further support of pyroptosis induction, both pan-caspase inhibitor and caspase-1 subfamily inhibitor, but not caspase-3 inhibitor, could sharply suppress gossypol-induced cell death. Other canonical pyroptotic inhibitors, including potassium chloride and N-acetyl-l-cysteine, could suppress ATP-induced pyroptosis but failed to in...Continue Reading

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Citations

Feb 2, 2018·Scientific Reports·Nathalia PizatoKelly Grace Magalhães
Feb 21, 2018·Journal of Neuroinflammation·Wei LiuLiangjun Zhang
Jul 6, 2019·Journal of Oncology·Ana Carolina Martínez-TorresCristina Rodríguez-Padilla
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Apr 19, 2020·International Immunopharmacology·Abdullah Al MamunJian Xiao
May 5, 2021·Journal of Physiology and Biochemistry·Xue GouYunman Li

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