Fractalkine-induced activation of the phosphatidylinositol-3 kinase pathway attentuates microglial activation in vivo and in vitro.

Trinity College Institute for Neuroscience, Physiology Department, Trinity College, Dublin 2, Ireland.
Journal of Neurochemistry (Impact Factor: 4.24). 08/2009; 110(5):1547-56. DOI: 10.1111/j.1471-4159.2009.06253.x
Source: PubMed

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.

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