{"title":"SPI1通过转录调节FOSL2表达影响a β1 - 42诱导的小胶质细胞介导的神经炎症","authors":"Jing Du , ZeXin An","doi":"10.1016/j.jneuroim.2025.578650","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 Aβ<sub>1</sub><sub>–</sub><sub>42</sub> induction. Furthermore, SPI1 knockdown or FOSL2 knockdown promoted M2 polarization in Aβ<sub>1</sub><sub>–</sub><sub>42</sub>-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 Aβ<sub>1</sub><sub>–</sub><sub>42</sub>-induced BV-2 cells by inhibiting FOSL2 expression and inactivating JAK2/STAT3 pathway.</div></div><div><h3>Conclusion</h3><div>SPI1 knockdown promoted M2 polarization of microglia, thereby suppressing neuroinflammation through suppression of the FOSL2/JAK2/STAT3 pathway, ultimately alleviating AD progression.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578650"},"PeriodicalIF":2.5000,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"SPI1 affects Aβ1–42-induced microglia-mediated neuroinflammation by transcriptionally regulating FOSL2 expression\",\"authors\":\"Jing Du , ZeXin An\",\"doi\":\"10.1016/j.jneuroim.2025.578650\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 Aβ<sub>1</sub><sub>–</sub><sub>42</sub> induction. Furthermore, SPI1 knockdown or FOSL2 knockdown promoted M2 polarization in Aβ<sub>1</sub><sub>–</sub><sub>42</sub>-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 Aβ<sub>1</sub><sub>–</sub><sub>42</sub>-induced BV-2 cells by inhibiting FOSL2 expression and inactivating JAK2/STAT3 pathway.</div></div><div><h3>Conclusion</h3><div>SPI1 knockdown promoted M2 polarization of microglia, thereby suppressing neuroinflammation through suppression of the FOSL2/JAK2/STAT3 pathway, ultimately alleviating AD progression.</div></div>\",\"PeriodicalId\":16671,\"journal\":{\"name\":\"Journal of neuroimmunology\",\"volume\":\"406 \",\"pages\":\"Article 578650\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-05-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of neuroimmunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0165572825001316\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neuroimmunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0165572825001316","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
SPI1 affects Aβ1–42-induced microglia-mediated neuroinflammation by transcriptionally regulating FOSL2 expression
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.
期刊介绍:
The Journal of Neuroimmunology affords a forum for the publication of works applying immunologic methodology to the furtherance of the neurological sciences. Studies on all branches of the neurosciences, particularly fundamental and applied neurobiology, neurology, neuropathology, neurochemistry, neurovirology, neuroendocrinology, neuromuscular research, neuropharmacology and psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays), are considered for publication.