Abstract
EBI2 is a G protein-coupled receptor activated by oxysterol 7α, 25-dihydroxycholesterol (7α25HC) and regulates T cell-dependant antibody response and B cell migration. We recently found EBI2 is expressed in human astrocytes, regulates intracellular signalling and modulates astrocyte migration. Here, we report that LPS treatment of mouse astrocytes alters mRNA levels of EBI2 and oxysterols suggesting that the EBI2 signalling pathway is sensitive to LPS-mediated immune challenge. We also find that conditioned media obtained from LPS-stimulated mouse astrocytes induces macrophage migration, which is inhibited by the EBI2 antagonist NIBR189. These results demonstrate a role for the EBI2 signalling pathway in astrocytes as a sensor for immune challenge and for communication with innate immune cells such as macrophages.
Highlights
The potential roles of the EBI2 signalling pathway molecules in disease and their potential uses as drug targets for Epstein-Barr virus (EBV) infection and EBV-mediated diseases as well as type-1-diabetes, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus has been recently discussed[16,17,18,19,20]
In agreement with the idea that EBI2 signalling may play a direct role in the central nervous system (CNS), we have reported that EBI2 is expressed in astrocytes, regulates astrocyte signalling, as well as astrocyte cell migration[22]
We first aimed to demonstrate that astrocytes stimulated with LPS could induce the migration of innate immune cells and, in this study, focused on their ability to regulate the migration of macrophages
Summary
The potential roles of the EBI2 signalling pathway molecules in disease and their potential uses as drug targets for Epstein-Barr virus (EBV) infection and EBV-mediated diseases as well as type-1-diabetes, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus has been recently discussed[16,17,18,19,20]. In agreement with the idea that EBI2 signalling may play a direct role in the central nervous system (CNS), we have reported that EBI2 is expressed in astrocytes, regulates astrocyte signalling, as well as astrocyte cell migration[22]. Another link between EBI2 signalling and brain disease comes from findings that CYP7B1/SPG5 mutations result in type 5 hereditary spastic paraplegia (hSPG5)[23]. Transwell system where macrophages (RAW264.7) were plated on recording electrodes (upper chamber) and mouse astrocyte conditioned media with or without 7α 25HC were added to the lower chamber. We examined if EBI2 signalling plays a role in the cellular communication of astrocytes with macrophages
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