Open AccessAzithromycin Protects Oligodendrocyte Progenitor Cells against Lipopolysaccharide-Activated Microglia-Induced Damage
Author(s) -
Sumana Ramarao,
Yi Pang,
Kathleen Carter,
Abhay Bhatt
Publication year - 2021
Publication title -
developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.893
H-Index - 82
eISSN - 1421-9859
pISSN - 0378-5866
DOI - 10.1159/000519874
Subject(s) - microglia , lipopolysaccharide , oligodendrocyte , immunology , neuroinflammation , inflammation , tumor necrosis factor alpha , chemistry , progenitor cell , myelin , biology , microbiology and biotechnology , stem cell , central nervous system , endocrinology
Oligodendrocyte progenitor cells (OPC) are the primary cellular targets of brain white matter injury (WMI) in very low-birth weight (VLBW) infants. Microglia plays a significant role in inflammation-induced WMI. Our previous study showed that lipopolysaccharide (LPS)-induced OPC damage is mediated by activated microglia in vitro. We hypothesized that azithromycin (AZ) could protect OPCs against LPS-induced cytotoxicity by blocking microglial activation. Highly enriched primary rat microglia and OPCs were treated with LPS. There were 4 groups: control, LPS + Veh, AZ, and LPS + AZ. Microglia conditioned medium (MCM) was used to determine inflammatory cytokines by enzyme-linked immunosorbent assay or subsequent treatment of OPCs. We found that AZ significantly suppressed TNF-α, IL-1β, and IL-6 in LPS+Veh-treated–microglial MCM and blocked microglial nuclear factor-κB p65 nuclear translocation. AZ prevented LPS-MCM-induced OPC death and improved OPC survival as measured by activated caspase-3 immunostaining and XTT assay, respectively. AZ ameliorated LPS-MCM-induced differentiation arrest and myelin basic protein deficit in oligodendrocytes. Our data suggest that AZ is a potent inhibitor for microglia activation and may hold the therapeutic potential for WMI in VLBW infants.