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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
SPI1 affects Aβ1-42-induced microglia-mediated neuroinflammation by transcriptionally regulating FOSL2 expression
1Department of Neurology, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei Province, China.
Background:
Microglia-induced-neuroinflammation contributes to Alzheimer's disease (AD) progression. SPI1 has been implicated in neuroinflammation and neuronal function and participated in AD progression. However, the underlying mechanism of SPI1 in microglia-induced neuroinflammation remains unclear.
Methods:
The levels of inflammatory factors in cell supernatant were determined using ELISA. Cellular morphology was observed through an inverted microscope. Gene and protein expression levels were detected using western blot, RT-qPCR and IF assay. The interaction between SPI1 and FOSL2 promoter was verified using dual luciferase experiment and ChIP.
Results:
A cell model of AD was successfully established, as evidenced by elevated inflammatory factors and altered cellular morphology. Besides, SPI1 and FOSL2 were elevated in BV2 cells by Aβ1-42 induction. Furthermore, SPI1 knockdown or FOSL2 knockdown promoted M2 polarization in Aβ1-42-induced BV-2 cells. Mechanistically, SPI1 bound to FOSL2 promoter to promote its transcriptional activity and expression of FOSL2. As expected, SPI1 knockdown facilitated M2 polarization in Aβ1-42-induced BV-2 cells by inhibiting FOSL2 expression and inactivating JAK2/STAT3 pathway.
Conclusion:
SPI1 knockdown promoted M2 polarization of microglia, thereby suppressing neuroinflammation through suppression of the FOSL2/JAK2/STAT3 pathway, ultimately alleviating AD progression.
Insights
Knocking down SPI1 promotes M2 microglia polarization, reducing neuroinflammation and potentially slowing Alzheimer's disease progression by inhibiting the FOSL2/JAK2/STAT3 pathway.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Microglia-driven neuroinflammation is a key factor in Alzheimer's disease (AD) progression.
- SPI1 is linked to neuroinflammation and neuronal function in AD, but its precise role is unclear.
Purpose of the Study:
- To elucidate the mechanism of SPI1 in microglia-induced neuroinflammation in Alzheimer's disease.
Main Methods:
- Established an Alzheimer's disease cell model using BV2 cells and Aβ1-42.
- Assessed inflammatory factors, cellular morphology, gene/protein expression (ELISA, Western blot, RT-qPCR, IF).
- Investigated SPI1-FOSL2 interaction using dual luciferase and ChIP assays.
Main Results:
- SPI1 and FOSL2 expression increased in Aβ1-42-induced BV2 cells.
- Knockdown of SPI1 or FOSL2 promoted M2 microglia polarization.
- SPI1 promotes FOSL2 expression by binding to its promoter, inactivating the JAK2/STAT3 pathway.
Conclusions:
- SPI1 knockdown enhances M2 microglia polarization, suppressing neuroinflammation.
- This suppression occurs via the FOSL2/JAK2/STAT3 pathway, potentially alleviating Alzheimer's disease progression.
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