机构：[1]College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan, China[2]Institute of Acupuncture and Homeostasis Regulation, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan, China[3]Acupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan, China[4]Neuroscience, College of Arts and Sciences, Boston University, Boston, MA 02215, USA[5]Department of Neurology, Dalian Municipal Central Hospital, Affiliated Hospital of Dalian Medical University, Dalian 116033, China
The immunological responses are a key pathological factor in Alzheimer's disease (AD). We hypothesized that microglial polarization alters microglia-astrocyte immune interactions in AD. M1 and M2 microglia were isolated from primary rat microglia and were confirmed to secrete pro-inflammatory and anti-inflammatory factors, respectively. Primary rat astrocytes were co-cultured with M1 or M2 microglial medium. M1 microglial medium increased astrocyte production of pro-inflammatory factors (interleukin [IL]-1β, tumor necrosis factor α and IL-6), while M2 microglial medium enhanced astrocyte production of anti-inflammatory factors (IL-4 and IL-10). To analyze the crosstalk between microglia and astrocytes after microglial polarization specifically in AD, we co-cultured astrocytes with medium from microglia treated with amyloid-β (Aβ) alone or in combination with other inflammatory substances. Aβ alone and Aβ combined with lipopolysaccharide/interferon-γ induced pro-inflammatory activity in M1 microglia and astrocytes, whereas IL-4/IL-13 inhibited Aβ-induced pro-inflammatory activity. Nuclear factor κB p65 was upregulated in M1 microglia and pro-inflammatory astrocytes, while Stat6 was upregulated in M2 microglia and anti-inflammatory astrocytes. These results provide direct evidence that microglial polarization governs communication between microglia and astrocytes, and that AD debris alters this crosstalk.
基金：
National Key Research and Development Program of China (No. 2019YFC1709001); The National Natural Science Foundation of China (No. 81704160, 81873383, 81873386); Chengdu University of Traditional Chinese Medicine “Xinglin Scholar” Discipline Talent Research and Improvement Plan (No. QNXZ2018001); Liaoning Revitalization Talents Program (No. XLYC1807083).
第一作者机构：[1]College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan, China[2]Institute of Acupuncture and Homeostasis Regulation, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan, China
通讯作者：
通讯机构：[2]Institute of Acupuncture and Homeostasis Regulation, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan, China[3]Acupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan, China
推荐引用方式(GB/T 7714)：
Xie Lushuang,Zhang Ning,Zhang Qun,et al.Inflammatory factors and amyloid β-induced microglial polarization promote inflammatory crosstalk with astrocytes.[J].AGING-US.2020,12:doi:10.18632/aging.103663.
APA：
Xie Lushuang,Zhang Ning,Zhang Qun,Li Chenyu,Sandhu Aaron F...&Yu Shuguang.(2020).Inflammatory factors and amyloid β-induced microglial polarization promote inflammatory crosstalk with astrocytes..AGING-US,12,
MLA：
Xie Lushuang,et al."Inflammatory factors and amyloid β-induced microglial polarization promote inflammatory crosstalk with astrocytes.".AGING-US 12.(2020)
