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

Area of Science:

• Neuroscience
• Immunology
• Molecular Biology

Background:

• The NLRP3 inflammasome activates caspase-1, releasing IL-1β and IL-18, crucial in host defense but implicated in inflammatory and neurodegenerative diseases.
• Overactivation of the NLRP3 inflammasome contributes to conditions like Alzheimer's and Parkinson's disease.

Purpose of the Study:

• To investigate the inhibitory effects of Sulforaphane (SFN) on NLRP3 inflammasome activation in murine microglial cells.
• To elucidate the molecular mechanisms by which SFN modulates NLRP3 inflammasome signaling.

Main Methods:

• Murine microglial cells were stimulated with LPS and ATP to activate the NLRP3 inflammasome.
• SFN's effects on IL-1β and IL-18 secretion and mRNA levels were measured.
• Caspase-1 activity, NLRP3 protein expression, and pyroptotic cell death were assessed.
• Western blot and caspase activity assays were employed.
• NF-κB nuclear translocation and Nrf2-mediated miRNA expression were analyzed.

Main Results:

• SFN significantly reduced IL-1β and IL-18 secretion and their mRNA levels in activated microglia.
• SFN suppressed the overexpression of cleaved caspase-1 and NLRP3 proteins.
• SFN inhibited caspase-1 dependent pyroptotic cell death.
• SFN suppressed NF-κB nuclear translocation and modulated Nrf2-mediated miRNA expression.

Conclusions:

• SFN effectively inhibits NLRP3 inflammasome activation, IL-1β/IL-18 secretion, and pyroptosis in murine microglia.
• SFN exerts its inhibitory effects by suppressing NF-κB nuclear translocation and modulating Nrf2-mediated miRNA expression.
• SFN represents a potential therapeutic agent for neuroinflammatory and neurodegenerative conditions associated with NLRP3 inflammasome overactivation.