The selective Nlrp3 inflammasome inhibitor Mcc950 attenuates lung ischemia-reperfusion injury

Biochemical and Biophysical Research Communications
Kai-Ying XuSi-Hua Wang

Abstract

Lung ischemia-reperfusion (IR) occurs in many circumstances and leads to impaired lung function. The NACHT, LRR and PYD domains-containing protein 3 (Nlrp3) inflammasome is reportedly activated during lung IR. Mcc950 is a recently developed Nlrp3 inhibitor. The aim of our study was to test the efficacy of Mcc950 on lung IR injury and to investigate the role of reactive oxygen species (ROS) in Nlrp3 inflammasome activation using a murine lung IR model. The results of the current study confirmed that Nlrp3 was upregulated and activated during lung IR, and inhibiting oxidative stress by the ROS scavenger edaravone attenuated Nlrp3 inflammasome activation. Mcc950 pretreatment significantly alleviated IR-induced lung injury by reducing production of the proinflammatory cytokines Il-1β and Il-18 and inhibiting neutrophil infiltration and cell apoptosis. Protein coimmunoprecipitation revealed that Mcc950 partially blocked the interaction between Nlrp3 and Nek7 (NimA-related protein kinase 7). Therefore, we conclude that ROS-dependent activation of the Nlrp3 inflammasome contributed to lung IR injury. Mcc950 significantly reduced lung IR injury by blocking Nlrp3 inflammasome activation, and the mechanism was partially attributed to inh...Continue Reading

Citations

Dec 28, 2018·Biology of Reproduction·Jonathan FaroNardhy Gomez-Lopez
Apr 17, 2020·Bioscience Trends·Ganglei LiuLianwen Yuan
Aug 1, 2020·Frontiers in Neurology·Gen LiGuobiao Liang
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