Fractalkine-induced activation of the phosphatidylinositol-3 kinase pathway attentuates microglial activation in vivo and in vitro.
Citation:Lyons A, Lynch AM, Downer EJ, Hanley R, O'Sullivan JB, Smith A, Lynch MA, Fractalkine-induced activation of the phosphatidylinositol-3 kinase pathway attentuates microglial activation in vivo and in vitro., Journal of Neurochemistry, 110, 5, 2009, 1547 - 1556
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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-1b. 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.
Science Foundation Ireland (SFI)
Type of material:Journal Article
Series/Report no:Journal of Neurochemistry
Availability:Full text available