Interleukin-18 protects rat primary cortical neurons by activating of the PI3K/Akt/NF-κB/CREB pathways
Interleukin-18 (IL-18),a member of the IL-1 family of cytokines,was initially identified as an interferon (IFN)-γ-inducing factor.IL-18 is expressed in both immune and non-immune cells and participates in the adjustment of multitude cellular functions.Nonetheless,the regulative roles of IL-18 in survival of cortical neurons have not been explored.The present study was conducted to investigate the effect of IL-18 on rat primary cortical neurons and elucidate the underlying mechanisms.We proved that recombinant rat interleukin-18 (rrIL-18) increased the expression of brain-derived neurotrophic factor (BDNF) in a dose and time-dependent manner even though it had no impact on neuron axon growth.Treatment with rrIL-18 (50 ng/ml) deactivated phosphatase and tensin homolog deleted on chromosome 10 (PTEN) by facilitating its phosphorylation,enhanced the expression of Phosphoinositide 3-OH kinase (PI3K) and phospho-Akt (p-Akt) to activate of the PI3K/Akt pathway.As its pivotal downstream pathways,nuclear factor-kappa B (NF-κB),cAMP-responsive element binding protein (CREB)/Bcl-2 and glycogen synthase kinase-3β (GSK-3β) were examined in further steps.Our data revealed that rrIL-18 stimulated NF-κB activation,improved phosphor-CREB (p-CREB) and anti-apoptotic Bcl-2 expression levels.But rrIL-18 had little or no effect on GSK-3β pathway.Besides,rrIL-18 increased levels of BDNF and Bcl-2/Bax ratio and decreased cleaved caspase-3 expression to protect cortical neurons from damage induced by oxygen-glucose deprivation (OGD).These results in vitro showed the accommodation of IL-18 in cortical neurons survival.Therefore,we suggested an important protective action of IL-18 on brain cortical neurons.
IL-18 cortical neurons PI3K/Akt NF-κB CREB/Bcl-2
Jia Zhou Fengfeng Ping Wenting Lv Junyi Feng Jing Song Jing Shang
Center for Drug Screening,China Pharmaceutical University,Nanjing 210009,China;State Key Laboratory of Natural Medicines,China Pharmaceutical University,China
国内会议
南宁
英文
1-22
2013-11-01（万方平台首次上网日期，不代表论文的发表时间）