Autophagy inhibition-enhanced assembly of the NLRP3 inflammasome is associated with cisplatin-induced acute injury to the liver and kidneys in rats

作者:Qu, Xiaoyu; Gao, Huan; Tao, Lina; Zhang, Yueming; Zhai, Jinghui; Song, Yanqing*; Zhang, Sixi*
来源:Journal of Biochemical and Molecular Toxicology, 2019, 33(1): e22208.
DOI:10.1002/jbt.22228

摘要

The nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome has a key role in the inflammatory response. We found that cisplatin (7.5, 15 mg/kg, IV) could induce acute injury to the liver and kidneys of rats. Western blot and immunohistochemical analyses showed that expression of NLRP3, caspase-1 and interleukin-1 beta was upregulated significantly in a dose-dependent manner after cisplatin exposure. Autophagy could inhibit NLRP3 expression and assembly of the NLRP3 inflammasome. Expression of light chain 3 II/I and p62 suggested that autophagy was inhibited during injury to the liver and kidneys. These data suggested that cisplatin might activate NLRP3 by inhibiting autophagy in the liver and kidneys of rats.