Bidirectional role of reactive oxygen species during inflammasome activation in acrolein-induced human EAhy926 cells pyroptosis

Abstract

Acrolein, a known toxin in tobacco smoke, has been demonstrated to be associated with inflammatory cardiovascular diseases, such as atherosclerosis. However, the definite mechanism of acrolein-induced inflammation remains unclear. Here, we report that acrolein induces reactive oxygen species (ROS) production in EAhy926 cells. Additionally, acrolein induces EAhy926 cells' inflammatory response and pyroptosis by activating NOD-like receptor protein 3 (NLRP3) inflammasome. Also, acrolein-induced cytotoxicity could be attenuated by N-acetyl-L-cysteine (NAC). Furthermore, acrolein upregulates the level of autophagy which can be reversed by NAC. Notably, the present study also indicates that autophagy inhibited by inhibitor 3-methyladenine (3MA) and siAtg7 exacerbate acrolein-induced NLRP3 inflammasome activation and pyroptosis. In summary, acrolein induced cytotoxicity by ROS-mediated NLRP3 inflammasome activation, and ROS upregulates the level of autophagy to inhibit the NLRP3 inflammasome excessive activation, indicating the bidirectional role of ROS in acrolein-induced cellular inflammation. Our results may provide novel mechanistic insights into acrolein-induced cardiovascular toxicity.

Keywords:

• Acrolein
• ROS
• pyroptosis
• autophagy
• inflammation

Author contributions

LJJ, XFL, and SSL designed the studies. TMQ, CTJ, and XCS participated in cell experiments. QNL completed the statistical analysis of the data. LPJ and TMQ wrote the manuscript. XCS, SSL, GY, and CZ revised the manuscript. All authors reviewed the manuscript. LJJ and XFL is the guarantor of the article.

Disclosure statement

The authors declare no competing financial interest.