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Interleukin-18 directly protects cortical neurons by activating PI3K/AKT/NF-κB/CREB pathways.
- Source :
-
Cytokine . Sep2014, Vol. 69 Issue 1, p29-38. 10p. - Publication Year :
- 2014
-
Abstract
- Interleukin-18 (IL-18), a member of the IL-1 family of cytokines, was initially identified as an interferon (IFN)-&#947-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 (50ng/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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10434666
- Volume :
- 69
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Cytokine
- Publication Type :
- Academic Journal
- Accession number :
- 97075151
- Full Text :
- https://doi.org/10.1016/j.cyto.2014.05.003