Caffeine Inhibits Activation of the NLRP3 Inflammasome via Autophagy to Attenuate Microglia-Mediated Neuroinflammation in Experimental Autoimmune Encephalomyelitis
| العنوان: | Caffeine Inhibits Activation of the NLRP3 Inflammasome via Autophagy to Attenuate Microglia-Mediated Neuroinflammation in Experimental Autoimmune Encephalomyelitis |
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| المؤلفون: | Si-Yuan Huang, Jinzhou Feng, Hui-Qi Wang, Qing-Zhe Hu, Lei Zhang, Gang Zhang, Rongrong Zhang, Yue Ma, Kai-Yi Song, Xinyue Qin, Xiu-Ming Guo, Yingchao Huo |
| المصدر: | Journal of Molecular Neuroscience. 72:97-112 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Encephalomyelitis, Autoimmune, Experimental, Inflammasomes, ATG5, Pharmacology, Proinflammatory cytokine, Mice, Cellular and Molecular Neuroscience, Caffeine, NLR Family, Pyrin Domain-Containing 3 Protein, Autophagy, medicine, Animals, Mechanistic target of rapamycin, Neuroinflammation, biology, Microglia, Chemistry, Experimental autoimmune encephalomyelitis, Inflammasome, General Medicine, medicine.disease, Mice, Inbred C57BL, medicine.anatomical_structure, Neuroinflammatory Diseases, biology.protein, medicine.drug |
| الوصف: | 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. |
| تدمد: | 1559-1166 0895-8696 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0a8887740e62332eb465232fae6a7f96 https://doi.org/10.1007/s12031-021-01894-8 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....0a8887740e62332eb465232fae6a7f96 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15591166 08958696 |
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