title: Fractalkine-induced activation of the phosphatidylinositol-3 kinase pathway attentuates microglial activation in vivo and in vitro.
abstract: Several neurodegenerative disorders are associated with evidence of inflammation, one feature of which is increased activation of microglia, the most likely cellular source of inflammatory cytokines like interleukin-1beta. It is now recognized that interaction of microglia with other cells contributes to maintenance of microglia in a quiescent state and the complementary distribution of the chemokine, fractalkine (CX(3)CL1) on neurons and its receptor (CX(3)CR1) on microglia, suggests that this interaction may play a role in modulating microglial activation. Here we demonstrate that both soluble and membrane-bound fractalkine attenuate lipopolysaccharide-induced microglial activation in vitro. We also show that fractalkine expression is reduced in the brain of aged rats and this is accompanied by an age-related increase in microglial activation. Treatment of aged rats with fractalkine attenuates the age-related increase in microglial activation and the evidence indicates that fractalkine-induced activation of the phosphatidylinositol-3 kinase pathway is required to maintain microglia in a quiescent state both in vivo and in vitro.
authors.affiliation: Trinity College Institute for Neuroscience, Physiology Department, Trinity College, Dublin 2, Ireland.
authors.forename: Anthony
authors.initials: A
authors.lastname: Lyons
authors.forename: Aileen M
authors.initials: AM
authors.lastname: Lynch
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Downer
authors.forename: Riona
authors.initials: R
authors.lastname: Hanley
authors.forename: Joan B
authors.initials: JB
authors.lastname: O'Sullivan
authors.forename: Andrew
authors.initials: A
authors.lastname: Smith
authors.forename: Marina A
authors.initials: MA
authors.lastname: Lynch
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D008070:Lipopolysaccharides / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D017628:Microglia / Q000201:enzymology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D012995:Solubility
chemical_list: D054428:Chemokine CX3CL1; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases