Argon mitigates post-stroke neuroinflammation by regulating M1/M2 polarization and inhibiting NF-κB/NLRP3 inflammasome signaling

• Published in: Journal of molecular cell biology 2023-04, Vol.14 (12)
• Main Authors: Xue, Ke, Qi, Mian, She, Tongping, Jiang, Zhenglin, Zhang, Yunfeng, Wang, Xueting, Wang, Guohua, Xu, Lihua, Peng, Bin, Liu, Jiayi, Song, Xinjian, Yuan, Yuan, Li, Xia
• Format: Article
• Language: English
• Subjects: Argon - metabolism; Argon - pharmacology; Argon - therapeutic use; Humans; Inflammasomes - metabolism; Inflammasomes - pharmacology; Inflammation - metabolism; Microglia - metabolism; Neuroinflammatory Diseases; NF-kappa B - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Signal Transduction
• ISSN: 1674-2788; 1759-4685
• DOI: 10.1093/jmcb/mjac077

ABSTRACT Neuroinflammation plays a vital role in cerebral ischemic stroke (IS). In the acute phase of IS, microglia are activated toward the pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. Argon, an inert gas, can reduce neuroinflammation and alleviate ischemia/reperfusion (I/R) injury. However, whether argon regulates M1/M2 polarization to protect against I/R injury as well as the underlying mechanism has not been reported. In this study, we analyzed the activation and polarization of microglia after I/R injury with or without argon administration and explored the effects of argon on NLRP3 inflammasome-mediated inflammation in microglia in vitro and in vivo. The results showed that argon application inhibited the activation of M1 microglia/macrophage in the ischemic penumbra and the expression of proteins related to NLRP3 inflammasome and pyroptosis in microglia. Argon administration also inhibited the expression and processing of IL-1β, a primary pro-inflammatory cytokine. Thus, argon alleviates I/R injury by inhibiting pro-inflammatory reactions via suppressing microglial polarization toward M1 phenotype and inhibiting the NF-κB/NLRP3 inflammasome signaling pathway. More importantly, we showed that argon worked better than the specific NLRP3 inflammasome inhibitor MCC950 in suppressing neuroinflammation and protecting against cerebral I/R injury, suggesting the therapeutic potential of argon in neuroinflammation-related neurodegeneration diseases as a potent gas inhibitor of the NLRP3 inflammasome signaling pathway.