| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
Toll-like receptor 4 activation by lipopolysaccharide (LPS) induced both death and survival in rat primary cultured microglia. Here, we investigated the mechanism of survival and purinergic modulation of dead cell phagocytosis and cytokine production in TLR4-activated microglia. LPS stimulation drastically induced the production of GM-CSF and up-regulated GM-CSF receptor signaling in surviving microglia. In addition, LPS-stimulated surviving microglia became motile and actively engulfed dead cells possibly through up-regulated P2Y2 receptors. Furthermore, Adenosine A2a receptors up-regulated by LPS stimulation suppressed TNF production. Purinergic activation promoted a marked elevation of protective cytokines such as activin-A. LPS-stimulated microglia protected neuronal cells in co-culture system. Together, TLR-4-activated long-lived microglia produce GM-CSF as an autocrine survival factor and may acquire protective phenotype through up-regulation of specific purinergic receptors.
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