title: The EBI2 signalling pathway plays a role in cellular crosstalk between astrocytes and macrophages.
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.
authors.affiliation: Drug Development, School of Medicine, Trinity College, Dublin, Ireland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Rutkowska
authors.affiliation: Drug Development, School of Medicine, Trinity College, Dublin, Ireland.
authors.forename: Sinead A
authors.initials: SA
authors.lastname: O'Sullivan
authors.affiliation: Analytical Sciences and Imaging, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Christen
authors.affiliation: Analytical Sciences and Imaging, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Sailer
authors.affiliation: Drug Development, School of Medicine, Trinity College, Dublin, Ireland.
authors.forename: Kumlesh K
authors.initials: KK
authors.lastname: Dev
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication; D002460:Cell Line; D002465:Cell Movement; D002851:Chromatography, High Pressure Liquid; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D000072376:Oxysterols / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry; D059467:Transcriptome
chemical_list: C543809:Gpr183 protein, mouse; D008070:Lipopolysaccharides; D000072376:Oxysterols; D043562:Receptors, G-Protein-Coupled