Interleukin-18 directly protects cortical neurons by activating PI3K/AKT/NF-κB/CREB pathways
| Autor: | Jing Shang, Feng-feng Ping, Jun-yi Feng, Wenting Lv, Jia Zhou |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Immunology
CREB Biochemistry Wortmannin chemistry.chemical_compound Glycogen Synthase Kinase 3 Phosphatidylinositol 3-Kinases GSK-3 Neurotrophic factors Immunology and Allergy Animals Phosphorylation Cyclic AMP Response Element-Binding Protein Molecular Biology Protein kinase B GSK3B Protein Kinase Inhibitors PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Brain-derived neurotrophic factor Cerebral Cortex Neurons Glycogen Synthase Kinase 3 beta biology Caspase 3 Brain-Derived Neurotrophic Factor Interleukin-18 NF-kappa B PTEN Phosphohydrolase Hematology Cell biology Rats Androstadienes Enzyme Activation Neuroprotective Agents chemistry Proto-Oncogene Proteins c-bcl-2 biology.protein Cancer research Proto-Oncogene Proteins c-akt |
| Zdroj: | Cytokine. 69(1) |
| ISSN: | 1096-0023 |
| Popis: | 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 effects of IL-18 on cortical neurons have not been explored. The present study was conducted to investigate the influence of IL-18 on rat primary cortical neurons and elucidate the underlying mechanisms. We proved that rrIL-18 increased the brain-derived neurotrophic factor (BDNF) expression in a time-dependent manner. 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 p-Akt, standing for the activation 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 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 protection of IL-18 on cortical neurons. And this direct neuroprotective effect of IL-18 is crippled by PI3K inhibitor wortmannin. |
| Databáze: | OpenAIRE |
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