|
|
 |
|
|
|
| |
|
|
| |
|
|
|
顆粒性白血球群落刺激因子可刺激Akt/GSK3β/NFκB的訊息傳遞以抑制內毒素引起之過渡活化的微膠細胞 G-CSF initiates Akt/GSK3β/NFκB signalings in suppressing the enhanced iNOS expression and NO production in LPS-activated BV-2 microglia
|
|
|
| 作者 |
 |
高品筠 |
| 學校系所 |
|
慈濟大學藥理暨毒理學研究所 |
| 地點 |
|
全臺 全部
|
| 研究內容 |
|
[ 摘要 ]
神經發炎（neuroinflammation）是造成神經病變及退化的重要成因之一。其中微膠細胞（microglia）過度活化扮演重要角色。微膠細胞活化造成超量的一氧化氮（NO）導致神經細胞的受損及傷亡。顆粒性白血球-群落刺激因子（granulocyte-colony stimulatin factor, G-CSF）是一種神經滋養因子，具神經保護及抗神經發炎的作用。然而在神經發炎中，G-CSF是否調節微膠細胞以達到保護神經細胞的作用尚未知曉。本研究發現在小鼠微膠細胞株BV-2的確有G-CSF的受體存在，暗示G-CSF可修飾微膠細胞的功能。內毒素會活化BV-2，增加誘導型一氧化氮合成�﹛]iNOS）的表現，使一氧化氮產量增加。此BV-2的活化可被G-CSF前處理降低。而G-CSF的前處理，會使磷酸化Akt，磷酸化glycogen synthase kinase 3β (GSK3β），以及細胞質nuclear factor-kappa B (NFκB)的增加。本研究首度證明G-CSF可以透過Akt/GSK3β/NFκB的訊息傳遞以抑制內毒素BV-2刺激的過渡活化。G-CSF在神經退化性疾病中是重要的神經保護藥物。
[ 英文摘要 ]
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. |
|
|
|
|
|
|
|
