| Summary: | 碩士 === 慈濟大學 === 藥理暨毒理學研究所 === 96 === Microglia activation enhances expression of the inducible NO synthase (iNOS) to over produce nitric oxide (NO), leading to neuronal damage. Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and anti-inflammatory effects. None is known about whether G-CSF may reduce the enhanced iNOS expression and NO production caused by the activated microglia. The investigator for the first time demonstrated G-CSF receptor on BV-2 microglia, indicating G-CSF may modulate function of the microglia. The microglia subjected to stimulation of lipopolysaccharide (LPS) enhanced iNOSmRNA/protein expression and NO production. This effect was suppressed by G-CSF pretreatment. The LPS treatment did not affect Akt expression, but increased p-GSK3β. Furthermore, it decreased cytosolic NFκB at 15 min, but increased at 30 min, 1 hr, and 12 hr. The G-CSF pretreatment caused greater increases in phosphorylated-Akt, phosphorylated-GSK3β, and cytosolic nuclear factor-kappa B (NFκB) at all time points. In conclusion, This is the first investigation demonstrating that G-CSF through activation of Akt/GSK3β and inactivation of NFκB suppresses LPS-induced microglial activation. This novel mechanism may reinforce the neuronally protective effect of G-CSF in neurological diseases.
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