Interleukin-10 release from astrocytes suppresses neuronal apoptosis via the TLR2/NFκB pathway in a neonatal rat model of hypoxic-ischemic brain damage

The biological function of interleukin-10 (IL-10) and the relationship between IL-10 secretion and the Toll-like receptor 2 (TLR2) expression levels in the central nervous system following hypoxic-ischemic brain damage (HIBD) are poorly understood. Here, we intend to elucidate the biological function and mechanism of IL-10 secretion following HIBD. In this study, we used a neonatal rat model of HIBD and found that rats injected with adeno-associated virus-IL-10-shRNA (short hairpin RNA) exhibited partially impaired learning and memory function compared to rats administered adeno-associated virus-control-shRNA. In vitro oxygen-glucose deprivation (OGD) induced IL-10 release from astrocytes but not from neurons. Pretreatment with exogenous recombinant IL-10 alleviated OGD-mediated apoptosis of neurons but not astrocytes. In addition, we also observed that hypoxic injury induced a marked increase in IL-10 expression in astrocytes as a result of activation of the TLR2/phosphorylated nuclear factor kappa B (p-NF kappa B) p65 signaling cascade; furthermore, this effect disappeared upon small interfering RNA targeting rat TLR2 gene (siTLR2) treatment. Pyrrolidinedithiocarbamate, an inhibitor of NF kappa B activation, reduced the IL-10 expression levels in both OGD-injured astrocytes in vitro and the hippocampi of HIBD rats in vivo but did not significantly affect TLR2 expression. Furthermore, a luciferase assay revealed that p-NF kappa B p65 could bind the - 1700/ - 1000 bp proximal region of the IL-10 gene promoter to regulate IL-10 secretion from astrocytes and that this interaction could be controlled by OGD treatment. These data suggest that HIBD induces IL-10 secretion from astrocytes to exert a paracrine-induced anti-apoptotic effect on injured neurons via the TLR2/NF kappa B signaling pathway, which may improve learning and memory dysfunction after ischemic injury.