دورية أكاديمية
Through Reducing ROS Production, IL-10 Suppresses Caspase-1-Dependent IL-1β Maturation, thereby Preventing Chronic Neuroinflammation and Neurodegeneration
| العنوان: | Through Reducing ROS Production, IL-10 Suppresses Caspase-1-Dependent IL-1β Maturation, thereby Preventing Chronic Neuroinflammation and Neurodegeneration |
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| المؤلفون: | Yun Gao, Dezhen Tu, Ru Yang, Chun-Hsien Chu, Jau-Shyong Hong, Hui-Ming Gao |
| المصدر: | International Journal of Molecular Sciences, Vol 21, Iss 2, p 465 (2020) |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | il-10, nlrp3 inflammasome, il-1β, neuroinflammation, ros, parkinson’s disease, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Chronic neuroinflammation contributes to the pathogenesis of Parkinson’s disease (PD). However, cellular and molecular mechanisms by which chronic neuroinflammation is formed and maintained remain elusive. This study aimed to explore detailed mechanisms by which anti-inflammatory cytokine interleukin-10 (IL-10) prevented chronic neuroinflammation and neurodegeneration. At 24 h after an intranigral injection of lipopolysaccharide (LPS), levels of NLRP3, pro-caspase-1, pro-IL-1β, active caspase-1, and mature IL-1β in the midbrain were much higher in IL-10−/− mice than wildtype mice. Mechanistically, IL-10−/− microglia produced more intracellular reactive oxygen species (iROS) and showed more profound activation of NADPH oxidase (NOX2) than wildtype microglia. Meanwhile, suppression of NOX2-derived iROS production blocked LPS-elicited caspase-1 activation and IL-1β maturation in IL-10−/− microglia in vitro and in vivo. One month after intranigral LPS injection, IL-10−/− mice revealed more profound microglial activation and dopaminergic neurodegeneration in the substantia nigra than wildtype mice. Importantly, such PD-like pathological changes were prevented by IL-1β neutralization. Collectively, IL-10 inhibited LPS-elicited production of NOX2-derived iROS thereby suppressing synthesis of NLRP3, pro-caspase-1 and pro-IL-1β and their activation and cleavage. By this mechanism, IL-10 prevented chronic neuroinflammation and neurodegeneration. This study suggested boosting anti-inflammatory effects of IL-10 and suppressing NLRP3 inflammasome activation could be beneficial for PD treatment. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 |
| Relation: | https://www.mdpi.com/1422-0067/21/2/465; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms21020465 |
| URL الوصول: | https://doaj.org/article/c600652c818e49afaff52b778b52686d |
| رقم الأكسشن: | edsdoj.600652c818e49afaff52b778b52686d |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 |
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| DOI: | 10.3390/ijms21020465 |