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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
SIRT1 decreases Aβ-induced IL-1β production by suppressing NLRP3 inflammasome activation and M1 microglial
Sifan Long1, Ruiqian Li2, Jiaming Yang1
1School of Medicine, Yunnan University, 2 Cuihu Bei Road, Kunming, Yunnan, 650091 People's Republic of China.
Abstract:
Microglia polarize into the proinflammatory M1 phenotype drive Alzheimer's disease (AD) pathogenesis through NLRP3 inflammasome-dependent maturation of interleukin (IL)-1β. Silent information regulator-1 (SIRT1) regulates a large number of cellular pathways and is related to aging and age-associated diseases, however, there were limited studies investigated whether SIRT1 can affect NLRP3 inflammasome and microglial activation and subsequent IL-1β production in AD. Here, we identified SIRT1 over-expression attenuated the release of IL-1β in amyloid-β (Aβ) treated microglia. Furthermore, our findings also revealed that NLRP3 inflammasome were less activated while the SIRT1 has been up-regulated. In addition, SIRT1 considerably alleviated the polarization of microglia toward to M1 phenotype mediated by Aβ, and the inhibitory on M1 polarization accompanied with the up-regulation of phosphorylated AMPK. This study demonstrated that SIRT1 can reduce IL-1β production by inhibiting the activation of NLRP3 and microglial phenotype toward M1, which suggesting SIRT1 may represent a potential strategy for modulating neuroinflammation in AD.
Insights
Silent information regulator-1 (SIRT1) reduces Alzheimer's disease (AD) inflammation by inhibiting microglial activation and IL-1β release. Upregulating SIRT1 may be a therapeutic strategy for AD neuroinflammation.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Microglia polarization to the M1 phenotype drives Alzheimer's disease (AD) pathogenesis via NLRP3 inflammasome-mediated IL-1β maturation.
- Silent information regulator-1 (SIRT1) is implicated in aging and age-related diseases, but its role in AD neuroinflammation is unclear.
Purpose of the Study:
- To investigate the effect of SIRT1 on NLRP3 inflammasome activation and microglial activation in AD.
- To determine if SIRT1 can modulate IL-1β production and microglial polarization in AD models.
Main Methods:
- Utilized amyloid-β (Aβ) treated microglia models.
- Assessed IL-1β release, NLRP3 inflammasome activation, and microglial M1 polarization.
- Investigated the role of SIRT1 and phosphorylated AMPK.
Main Results:
- SIRT1 over-expression attenuated IL-1β release in Aβ-treated microglia.
- Increased SIRT1 levels correlated with reduced NLRP3 inflammasome activation.
- SIRT1 alleviated Aβ-induced M1 microglial polarization, associated with increased phosphorylated AMPK.
Conclusions:
- SIRT1 inhibits NLRP3 inflammasome activation and M1 microglial polarization, thereby reducing IL-1β production.
- SIRT1 represents a potential therapeutic target for modulating neuroinflammation in Alzheimer's disease.
