title: SR-A regulates the inflammatory activation of astrocytes.
abstract: Scavenger receptor Class A (SR-A) participates in the regulation of inflammatory processes against pathogens and in inflammatory stimulation. We have recently demonstrated the presence of SR-A in astrocytes, but its participation in their inflammatory response is unknown. Astrocytes regulate neuroinflammation through the regulation of microglial cell activation and the production of cytokines, neurotrophic factors, and reactive species. Using astrocytes from SR-A(-/-) mice in culture, we assessed the participation of SR-A in their inflammatory activation, evaluating the activation of IκB/NF-κB and MAPK signaling pathways and the production of nitric oxide (NO) and IL-1β in response to SR-A ligands. In SR-A(-/-) astrocytes, lipopolysaccharide (LPS) induced higher levels of NO and reduced levels of IL-1β compared to SR-A(+/+) cells. In addition, SR-A(-/-) astrocytes had a reduced basal and LPS-stimulated JNK phosphorylation, and a delayed activation on IκB/NF-κB signaling pathway in response to LPS. Moreover, inhibition of the ERK pathway reduced NO production by SR-A(-/-) cells, suggesting that this signaling pathway modulated LPS-induced NO production, an effect that depended on the presence of SR-A. Our results suggest that SR-A participates in the modulation of signaling pathways involved in the production of soluble molecules implicated in the neuroinflammatory response.
authors.affiliation: Departamento de Neurología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Murgas
authors.forename: F A
authors.initials: FA
authors.lastname: Cornejo
authors.forename: G
authors.initials: G
authors.lastname: Merino
authors.forename: R
authors.initials: R
authors.lastname: von Bernhardi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D051117:Scavenger Receptors, Class A; D009569:Nitric Oxide