[en] The NLRP3 inflammasome is a multiprotein complex that activates caspase-1 and triggers the release of the proinflammatory cytokines IL-1β and IL-18 in response to diverse signals. Although inflammasome activation plays critical roles against various pathogens in host defense, overactivation of inflammasome contributes to the pathogenesis of inflammatory diseases, including acute CNS injuries and chronic neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. In the current study, we demonstrated that Sulforaphane (SFN), a dietary natural product, inhibits NLRP3 inflammasome mediated IL-1β and IL-18 secretion and pyroptosis in murine microglial cells. SFN decreased the secretion of IL-1β and IL-18, and their mRNA levels in LPS primed microglia triggered by ATP. SFN suppressed the overexpression of cleaved caspase-1 and NLRP3 protein expressions as measured by caspase activity assay and western blot, respectively. SFN also prevented caspase-1 dependent pyroptotic cell death in microglia. Our data indicate that SFN suppresses NLRP3 inflammasome via the inhibition of NF-κB nuclear translocation and Nrf2 mediated miRNAs expression modulation in murine microglia.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Tufekci, Kemal Ugur ; Izmir Biomedicine and Genome Center (IBG), Izmir, Turkey, Vocational School of Health Services, Izmir Democracy University, Izmir, Turkey
Ercan, Ilkcan ; Izmir Biomedicine and Genome Center (IBG), Izmir, Turkey, Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey
Isci, Kamer Burak; Izmir Biomedicine and Genome Center (IBG), Izmir, Turkey, Department of Neuroscience, Health Science Institute, Dokuz Eylul University, Izmir, Turkey
Olcum, Melis ; Izmir Biomedicine and Genome Center (IBG), Izmir, Turkey
TASTAN, Bora ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuroinflammation Group ; Izmir Biomedicine and Genome Center (IBG), Izmir, Turkey, Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey
Gonul, Ceren Perihan ; Izmir Biomedicine and Genome Center (IBG), Izmir, Turkey, Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey
Genc, Kursad ; Department of Neuroscience, Health Science Institute, Dokuz Eylul University, Izmir, Turkey
Genc, Sermin; Izmir Biomedicine and Genome Center (IBG), Izmir, Turkey, Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey, Department of Neuroscience, Health Science Institute, Dokuz Eylul University, Izmir, Turkey. Electronic address: sermin.genc@deu.edu.tr
External co-authors :
yes
Language :
English
Title :
Sulforaphane inhibits NLRP3 inflammasome activation in microglia through Nrf2-mediated miRNA alteration.
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