[en] Ethyl pyruvate is a molecule with anti-inflammatory and pro-metabolic effects. Ethyl pyruvate has been shown to ameliorate the clinical and pathological findings of neurodegenerative diseases such as Alzheimer's and Parkinson's Diseases in rodents. Its anti-inflammatory and neuroprotective effects are widely investigated in animal and cellular models. Our study aimed to investigate the mechanism of the impact of Ethyl pyruvate on NLRP3 inflammasome activation in the N9 microglial cell line. Our results indicated that ethyl pyruvate significantly suppressed LPS and ATP-induced NLRP3 inflammasome activation, decreased active caspase-1 level, secretion of IL-1β and IL-18 cytokines, and reduced the level of pyroptotic cell death resulting from inflammasome activation. Furthermore, ethyl pyruvate reduced the formation of total and mitochondrial ROS and suppressed inflammasome-induced HMGB1 upregulation and nuclear NF-κB translocation and reversed the inflammasome activation-induced miRNA expression profile for miR-223 in N9 cells. Our study suggests that ethyl pyruvate effectively suppresses the NLRP3 inflammasome activation in microglial cells regulation by miR-223 and NF-κB/HMGB1 axis.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Olcum, Melis; Izmir Biomedicine and Genome Center, Izmir 35340, Turkey
Tufekci, Kemal Ugur ; Vocational School of Health Services, Izmir Democracy University, Izmir 35290, Turkey
Durur, Devrim Yagmur; Izmir Biomedicine and Genome Center, Izmir 35340, Turkey ; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey
TASTAN, Bora ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuroinflammation Group ; Izmir Biomedicine and Genome Center, Izmir 35340, Turkey ; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey
Gokbayrak, Irem Nur; Department of Neuroscience, Health Science Institute, Dokuz Eylul University, Izmir 35340, Turkey
Genc, Kursad; Department of Neuroscience, Health Science Institute, Dokuz Eylul University, Izmir 35340, Turkey
Genc, Sermin ; Izmir Biomedicine and Genome Center, Izmir 35340, Turkey ; Department of Neuroscience, Health Science Institute, Dokuz Eylul University, Izmir 35340, Turkey
External co-authors :
yes
Language :
English
Title :
Ethyl Pyruvate Attenuates Microglial NLRP3 Inflammasome Activation via Inhibition of HMGB1/NF-κB/miR-223 Signaling.
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