Research Paper Volume 12, Issue 22 pp 22538—22549
Inflammatory factors and amyloid β-induced microglial polarization promote inflammatory crosstalk with astrocytes
- 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
Received: April 27, 2020 Accepted: June 17, 2020 Published: November 16, 2020https://doi.org/10.18632/aging.103663
How to Cite
Copyright: © 2020 Xie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.