NLRP3 Knockout Protects against Lung Injury Induced by Cerebral Ischemia-Reperfusion.

Abstract

Methods:

C57/BL6 wild-type (WT) and NLRP3-KO mice were used to construct middle cerebral artery occlusion (MCAO) models. 2,3,5-Triphenyltetrazolium chloride (TTC) was used to evaluate brain damage, and neurological deficits were assessed. Then, lung tissue injury was examined in the different groups of mice by hematoxylin-eosin (HE) staining. Inflammation (macrophage and neutrophil infiltration, NLRP3-associated inflammatory molecules) and oxidative stress (reactive oxygen species, ROS) in the lungs were comprehensively examined by immunofluorescence staining and Western blotting.

Results:

First, our findings demonstrated that NLRP3 knockout had a protective effect against cerebral ischemia-reperfusion injury after MCAO. Second, by reducing brain damage after MCAO, lung inflammation was also alleviated. Immunofluorescence staining showed that NLRP3-KO-MCAO mice had reduced inflammatory effector molecule (caspase-1 and IL-1β) expression and macrophage and neutrophil infiltration in the lung, as well as remissive oxidative stress state in the lung, compared with WT-MCAO mice. We also observed a decrease in phosphorylated p65 (p-p65) (an NF-κB factor) in NLRP3-KO-MCAO mice, suggesting that the NF-κB pathway was involved in the protective effect of NLRP3 gene knockout on stroke-induced lung injury.

Conclusions:

NLRP3 inflammasome knockout not only is beneficial for cerebral ischemia-reperfusion injury but also reduces the severity of poststroke lung injury by reducing brain damage. It has been confirmed that there is a relationship between central insult and peripheral organ injury, and protecting the brain can prevent peripheral organ damage.

• Authors: Qingxue Xu, Yingze Ye, Zhuo Wang, Hua Zhu, Yina Li, Jin Wang, Wenwei Gao, Lijuan Gu
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2022 Pg. 6260102 ( 2022) ISSN: 1942-0994 [Electronic] United States
• PMID: 35432726 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Qingxue Xu et al.

Chemical References

• Inflammasomes
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse

Topics

• Animals
• Brain Injuries
• Brain Ischemia (genetics, metabolism)
• Infarction, Middle Cerebral Artery (metabolism)
• Inflammasomes (metabolism)
• Lung Injury
• Mice
• Mice, Knockout
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Reperfusion
• Reperfusion Injury (metabolism)