Heat stress induces IL-1β and IL-18 overproduction via ROS-activated NLRP3 inflammasome: implication in neuroinflammation in mice with heat stroke

Author:

Du Guoqiang1,Yang Zixi2,Wen Yin3,Li Xusheng4,Zhong Wenhong3,Li Zhuo3,Zhang Shiying3,Luo Ensi5,Ding Hongguang4,Li Weifeng4

Affiliation:

1. Department of Emergency Medicine, Luoding People’s Hospital, Yunfu

2. College of Continuing Education, Guangdong Medical University, Zhanjiang

3. Department of Critical Care Medicine

4. Department of Emergency Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou

5. Department of Endocrinology, Binhaiwan Central Hospital of Dongguan, Dongguan Hospital Affiliated to Medical College of Jinan University, Dongguan, China

Abstract

Heat stroke induced cerebral damage via neuroinflammation. This study aimed to approach whether heat stress would promote NOD-like receptor protein 3 (NLRP3) inflammasome via reactive oxygen species (ROS). The mice were randomly divided into the sham group, the heat stress group, and the heat stress + TEMPOL (ROS scavenger) group. And the NLRP3−/− mice were applied and divided into the NLRP3−/− + sham group and the NLRP3−/− + heat stress group. Furthermore, the BV2 cells were divided into four groups following the intervention measures: the heat stress + TEMPOL group, the heat stress + Z-VAD-FMK (caspase-1 inhibitor) group, the heat stress group, and the control group. ROS levels were examined. The expression levels of NLRP3, caspase-1, IL-1β, and IL-18 were detected by western blotting and double immunofluorescence. We found that heat stress attack induced excessive ROS in microglia and subsequently activated NLRP3 inflammasome in both mice and BV2 cells. When ROS scavenged, the expression level of NLRP3 was downregulated. Furthermore, with NLRP3 inflammasome activation, the expression levels of caspase-1, IL-1β, and IL-18 were increased. In NLRP3−/− mice, however, the caspase-1, IL-1β, and IL-18 were significantly declined. Further experiments showed that pretreatment of caspase-1 inhibitor decreased the expression levels of IL-1β and IL-18. These results suggest that heat stress attack caused neuroinflammation via excessive ROS activating the NLRP3 inflammasome in microglia cells.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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