Caffeine Inhibits Activation of the NLRP3 Inflammasome via Autophagy to Attenuate Microglia-Mediated Neuroinflammation in Experimental Autoimmune Encephalomyelitis.

Autor: Wang HQ; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.; Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China., Song KY; Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China., Feng JZ; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China., Huang SY; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China., Guo XM; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China., Zhang L; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China., Zhang G; Cerebravascular Disease Department. Number 98, The First People's Hospital of Zunyi, (The third affiliated hospital of Zunyi Medical University), Fenghuang Road, Zunyi, Guizhou Province, 563000, China., Huo YC; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China., Zhang RR; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China., Ma Y; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China., Hu QZ; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China., Qin XY; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China. qinxinyue2019168@sina.com.
Jazyk: angličtina
Zdroj: Journal of molecular neuroscience : MN [J Mol Neurosci] 2022 Jan; Vol. 72 (1), pp. 97-112. Date of Electronic Publication: 2021 Sep 03.
DOI: 10.1007/s12031-021-01894-8
Abstrakt: The activation of microglia is an important cause of central nervous system (CNS) inflammatory cell infiltration and inflammatory demyelination in experimental autoimmune encephalomyelitis (EAE). Furthermore, the proinflammatory response induced by the NLR family pyrin domain containing 3 (NLRP3) inflammasome can be amplified in microglia after NLRP3 inflammasome activation. Autophagy is closely related to the inflammatory response. Caffeine exerts anti-inflammatory and autophagy-stimulating effects, but the specific mechanism remains unclear. This study examined the mechanism underlying the anti-inflammatory effect of caffeine on EAE. In this study, C57BL/6 mice were immunized to induce EAE and treated with caffeine to observe its effect on prognosis. The effects of caffeine on autophagy and inflammation were also analysed in mouse primary microglia (PM) and the BV2 cell line. The data demonstrated that caffeine reduced the clinical score, the infiltration of inflammatory cells, the demyelination level, and the activation of microglia in EAE mice. Furthermore, caffeine increased the LC3-II/LC3-I levels and decreased the NLRP3 and P62 levels in EAE mice, whereas the autophagy inhibitor 3-methylamine (3-MA) blocked these effects. In vitro, caffeine promoted autophagy by suppressing the mechanistic target of rapamycin (mTOR) pathway and inhibited activation of the NLRP3 inflammasome. However, autophagy-related gene 5 (ATG5)-specific siRNA abolished the anti-inflammatory effect of caffeine treatment in PM and BV2 cells. Taken together, these data suggest that caffeine exerts a newly discovered effect on EAE by reducing NLRP3 inflammasome activation via the induction of autophagy in microglia.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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