Sulforaphane inhibits NLRP3 inflammasome activation in microglia through Nrf2-mediated miRNA alteration.

Tufekci K. U., Ercan I., Isci K. B., Olcum M., Tastan B., Gonul C. P., ...Daha Fazla

Immunology letters, cilt.233, ss.20-30, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 233
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.imlet.2021.03.004
  • Dergi Adı: Immunology letters
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.20-30
  • Anahtar Kelimeler: Sulforaphane, NLRP3 inflammasome, Microglia, Nrf2, Pyroptosis, microRNA, KAPPA-B, EXPRESSION, MICRORNA
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

The NLRP3 inflammasome is a multiprotein complex that activates caspase-1 and triggers the release of the proinflammatory cytokines IL-1 beta 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-1 beta and IL-18 secretion and pyroptosis in murine microglial cells. SFN decreased the secretion of IL-1 beta 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-kappa B nuclear translocation and Nrf2 mediated miRNAs expression modulation in murine microglia.