Fractalkine-induced activation of the phosphatidylinositol-3 kinase pathway attentuates microglial activation in vivo and in vitro |
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Authors: | Anthony Lyons Aileen M Lynch Eric J Downer Riona Hanley Joan B O'Sullivan rew Smith Marina A Lynch |
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Institution: | Trinity College Institute for Neuroscience, Physiology Department, Trinity College, Dublin, Ireland |
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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-1β. 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 (CX3CL1) on neurons and its receptor (CX3CR1) 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 . |
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Keywords: | cytokines fractalkine microglia neuroinflammation phosphatidylinositol-3 kinase signaling and aging |
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