IL-10 directly protects cortical neurons by activating PI-3 kinase and STAT-3 pathways

IL-10 reduces pro-inflammatory responses after ischemic stroke primarily by acting on glia and endothelium, but relatively little is known about the direct effects of IL-10 on cortical neurons, which are often damaged in stroke. We found by PCR and immunohistochemistry that cortical neurons express IL-10 receptor. Treatment of primary cortical neurons in culture with IL-10 increased neuronal survival after exposure to oxygen-glucose deprivation (OGD) or glutamate toxicity. IL-10 also induced phosphorylation of AKT in cortical neurons. Pretreatment with the specific PI-3K inhibitor, wortmannin, attenuated IL-10 mediated neuroprotection against OGD and glutamate. In addition, IL-10 induced STAT-3 phosphorylation. Pre-treatment with a functional blocking antibody to the IL-10 receptor reduced both Stat-3 and AKT phosphorylation and blocked IL-10 mediated protection of cortical neurons. These data suggest that IL-10 provides neuroprotection by acting via IL-10 receptor and PI3K/AKT and STAT-3 signal transduction pathways. (c) 2010 Elsevier B.V. All rights reserved.