Microglia-mediated neuroinflammation plays a crucial role in ischemic stroke;consequently,understanding its regulation could facilitate the development of therapies for ischemic stroke.Chemerin 15,a 15-amino acid pept...Microglia-mediated neuroinflammation plays a crucial role in ischemic stroke;consequently,understanding its regulation could facilitate the development of therapies for ischemic stroke.Chemerin 15,a 15-amino acid peptide derived from chemerin,exerts powerful anti-inflammatory effects through ChemR23,modulates macrophage polarization,and diminishes inflammatory cytokine expression in peripheral inflammation models.However,its effects on microglia and stroke remain unclear.In this study,we used an in vitro oxygen/glucose deprivation BV2 cell model and a mouse model of ischemia-reperfusion injury to investigate the role of chemerin 15 in stroke and the underlying mechanisms.We co-cultured BV2 microglial cells with HT-22 hippocampal neurons and observed that chemerin 15 reduced apoptosis in HT-22 cells.Furthermore,we found that chemerin 15 binds to the ChemR23 receptor on the cell surface,inducing its internalization.This process regulated the activity of adenosine 5ʹ-monophosphate-activated protein kinase and inhibited its downstream target nuclear factor kappa B.These effects could be reversed by treatment with α-NETA,a ChemR23 inhibitor.In mice with ischemia-reperfusion injury,chemerin 15 modulated microglial polarization,reduced infarct volume and neuronal apoptosis,and facilitated cognitive and neurological function recovery.Our findings suggest that chemerin 15 suppresses the microglia-mediated inflammatory response,decreases neuronal apoptosis,and enhances long-term neurological function recovery by inducing ChemR23 internalization and regulating the adenosine 5ʹ-monophosphate-activated protein kinase/nuclear factor kappa B signaling pathway.展开更多
目的:探究chemerin对银屑病患者外周血辅助性T淋巴细胞9(helper T cells 9,Th9)/调节性T淋巴细胞(regulatory T cells,Treg)免疫平衡的调节作用及其潜在的机制。方法:选取25例银屑病患者和20例健康志愿者,采用磁珠分离法分离出受试者外...目的:探究chemerin对银屑病患者外周血辅助性T淋巴细胞9(helper T cells 9,Th9)/调节性T淋巴细胞(regulatory T cells,Treg)免疫平衡的调节作用及其潜在的机制。方法:选取25例银屑病患者和20例健康志愿者,采用磁珠分离法分离出受试者外周血中CD4+T细胞,行实时RT-PCR和ELISA检测细胞中chemerin和其受体chemR23的表达;用不同浓度的chemerin(50,100,150,200 ng/mL)分别处理从健康志愿者外周血分离得到的CD4+T细胞,行MT T比色法检测细胞活力以筛选最适浓度;采用ELISA检测炎性细胞因子水平;行流式细胞术检测Th9和Treg细胞数。结果:与对照相比,银屑病患者外周血中chemerin和chemR23的表达均显著增加,T h 9/Treg比例明显上升(均P<0.05);选取最适浓度150 ng/mL的chemerin处理CD4+T细胞后,细胞中白细胞介素(IL)-6,IL-9和IL-17的水平均显著增加,Th9/Treg比例明显上升(均P<0.05),而chemR23沉默可反转chemerin对CD4+T细胞的上述作用(均P<0.05)。结论:Chemerin通过chemR23调节银屑病患者外周血CD4+T淋巴细胞中的T h 9/Treg细胞免疫平衡。展开更多
基金Gulin-Southwest Medical University Hospital Strategic Cooperation Project,No.2022 GLXNYDFY10(to JL)Suining First People’s Hospital-Southwest Medical University Cooperation Project,No.2021SNXNYD06(to JL)+2 种基金Postdoctoral Research Foundation of China,No.2021M692285(to LW)Key Research and Development Project of the Science and Technology Department of Sichuan Province,No.2022YFS0318(to LW)Post-Doctor Research Project of West China Hospital,Sichuan University,No.2021HXBH083(to LW).
文摘Microglia-mediated neuroinflammation plays a crucial role in ischemic stroke;consequently,understanding its regulation could facilitate the development of therapies for ischemic stroke.Chemerin 15,a 15-amino acid peptide derived from chemerin,exerts powerful anti-inflammatory effects through ChemR23,modulates macrophage polarization,and diminishes inflammatory cytokine expression in peripheral inflammation models.However,its effects on microglia and stroke remain unclear.In this study,we used an in vitro oxygen/glucose deprivation BV2 cell model and a mouse model of ischemia-reperfusion injury to investigate the role of chemerin 15 in stroke and the underlying mechanisms.We co-cultured BV2 microglial cells with HT-22 hippocampal neurons and observed that chemerin 15 reduced apoptosis in HT-22 cells.Furthermore,we found that chemerin 15 binds to the ChemR23 receptor on the cell surface,inducing its internalization.This process regulated the activity of adenosine 5ʹ-monophosphate-activated protein kinase and inhibited its downstream target nuclear factor kappa B.These effects could be reversed by treatment with α-NETA,a ChemR23 inhibitor.In mice with ischemia-reperfusion injury,chemerin 15 modulated microglial polarization,reduced infarct volume and neuronal apoptosis,and facilitated cognitive and neurological function recovery.Our findings suggest that chemerin 15 suppresses the microglia-mediated inflammatory response,decreases neuronal apoptosis,and enhances long-term neurological function recovery by inducing ChemR23 internalization and regulating the adenosine 5ʹ-monophosphate-activated protein kinase/nuclear factor kappa B signaling pathway.
文摘目的:探究chemerin对银屑病患者外周血辅助性T淋巴细胞9(helper T cells 9,Th9)/调节性T淋巴细胞(regulatory T cells,Treg)免疫平衡的调节作用及其潜在的机制。方法:选取25例银屑病患者和20例健康志愿者,采用磁珠分离法分离出受试者外周血中CD4+T细胞,行实时RT-PCR和ELISA检测细胞中chemerin和其受体chemR23的表达;用不同浓度的chemerin(50,100,150,200 ng/mL)分别处理从健康志愿者外周血分离得到的CD4+T细胞,行MT T比色法检测细胞活力以筛选最适浓度;采用ELISA检测炎性细胞因子水平;行流式细胞术检测Th9和Treg细胞数。结果:与对照相比,银屑病患者外周血中chemerin和chemR23的表达均显著增加,T h 9/Treg比例明显上升(均P<0.05);选取最适浓度150 ng/mL的chemerin处理CD4+T细胞后,细胞中白细胞介素(IL)-6,IL-9和IL-17的水平均显著增加,Th9/Treg比例明显上升(均P<0.05),而chemR23沉默可反转chemerin对CD4+T细胞的上述作用(均P<0.05)。结论:Chemerin通过chemR23调节银屑病患者外周血CD4+T淋巴细胞中的T h 9/Treg细胞免疫平衡。
