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Interleukin‐10 release from astrocytes suppresses neuronal apoptosis via the TLR 2/ NF κB pathway in a neonatal rat model of hypoxic‐ischemic brain damage
Author(s) -
He Mu Lan,
Lv Ze Yu,
Shi Xia,
Yang Ting,
Zhang Yun,
Li TingYu,
Chen Jie
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14126
Subject(s) - small hairpin rna , tlr2 , biology , apoptosis , astrocyte , signal transduction , microbiology and biotechnology , small interfering rna , receptor , chemistry , endocrinology , central nervous system , tlr4 , transfection , cell culture , gene knockdown , biochemistry , genetics
Abstract The biological function of interleukin‐10 ( IL ‐10) and the relationship between IL ‐10 secretion and the Toll‐like receptor 2 ( TLR 2) 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‐sh RNA (short hairpin RNA ) exhibited partially impaired learning and memory function compared to rats administered adeno‐associated virus‐control‐sh RNA . 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 TLR 2/phosphorylated nuclear factor kappa B (p‐ NF κB) p65 signaling cascade; furthermore, this effect disappeared upon small interfering RNA targeting rat TLR 2 gene (si TLR 2) treatment. Pyrrolidinedithiocarbamate, an inhibitor of NF κB 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 TLR 2 expression. Furthermore, a luciferase assay revealed that p‐ NF κB 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 TLR 2/ NF κB signaling pathway, which may improve learning and memory dysfunction after ischemic injury.