IL-10 produces a dual effect on OGD-induced neuronal apoptosis of cultured cortical neurons via the NF-κB pathway.

As a classic immunoregulatory cytokine, interleukin-10 (IL-10) can provide in vivo and in vitro neuroprotection respectively during cerebral ischemia and after the oxygen-glucose deprivation (OGD)-induced injury. However, its role in cortical neuronal survival at different post-ischemic phases remains unclear. The current study found that IL-10 had distinct effects on the neuronal apoptosis at different OGD stages: at an early stage after OGD, IL-10 promoted the OGD-induced neuronal apoptosis in the cultured primary cortical neurons by activating p65 subunit, which up-regulated Bax expression and down-regulated Bcl-xL expression; at a late OGD stage, however, it attenuated the OGD-induced neuronal apoptosis by activating c-Rel, which up-regulated Bcl-xL expression and down-regulated Bax expression. The early-stage pro-apoptosis and late-stage anti-apoptosis were both partly abolished by PDTC, an NF-κB inhibitor, and promoted by PMA, an NF-κB activator. The optimal anti-apoptotic effect appeared when the cultured neurons were treated with IL-10 at 9-24 h after OGD. Taken together, our findings suggest that IL-10 exerts a dual effect on the survival of the cultured neurons by activating the NF-κB pathway at different stages after OGD injury and that PMA treatment at a late stage can facilitate the IL-10-conferred neuroprotection against OGD-induced neuronal injury.