Methane limit LPS-induced NF-κB/MAPKs signal in macrophages and suppress immune response in mice by enhancing PI3K/AKT/GSK-3β-mediated IL-10 expression.
Methane limit LPS-induced NF-κB/MAPKs signal in macrophages and suppress immune response in mice by enhancing PI3K/AKT/GSK-3β-mediated IL-10 expression.
复制标题
甲烷通过增强 PI3K/AKT/GSK-3 β 介导的 IL-10 表达来限制巨噬细胞中 LPS 诱导的 NF-κ B/MAPK 信号并抑制小鼠的免疫反应
DOI：
10.1038/srep29359
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发表时间：
2016-07-11
影响因子：
4.6
通讯作者：
Deng X
中科院分区：
文献类型：
--
作者：
Zhang X;Li N;Shao H;Meng Y;Wang L;Wu Q;Yao Y;Li J;Bian J;Zhang Y;Deng X
脓毒症和自身免疫性结肠炎等炎症性疾病的特征是免疫系统的过度激活和抗炎反应的抵消，仍然是世界范围内的主要健康问题。新的证据表明，甲烷对许多动物模型具有保护作用，例如缺血再灌注损伤和糖尿病相关疾病。甲烷是否可以调节炎症性疾病仍然很大程度上未知。在这里，我们表明，富甲烷盐水 (MS) ip 处理 (16ml/kg) 通过减少 TNF-α 和 IL-6 的产生，减轻了小鼠内毒素休克、细菌引起的败血症和葡聚糖硫酸钠引起的结肠炎。在 MS 处理的巨噬细胞中，LPS 诱导的 NF-κb/MAPK 激活减弱。有趣的是，MS 治疗显着提高了体外和体内 IL-10 的水平。 IL-10 的中和消除了 MS 的治疗效果。此外，抗 IL10 阻断部分恢复了 MS 介导的 NF-κb/MAPK 磷酸化减弱。我们进一步发现 MS 导致 GSK-3β 和 AKT 的磷酸化显着增强，这两者均介导 Il-10 的释放。此外，抑制 PI3K 会减弱 MS 介导的 p-GSK-3β 和 IL-10 的产生，并逆转 LPS 响应下的 NF-κb/MAPK 激活受到抑制。我们的结果揭示了甲烷的新作用和机制，并支持 MS 作为先天性炎症疾病治疗方法的潜在价值。
Inflammatory diseases such as sepsis and autoimmune colitis, characterized by an overwhelming activation of the immune system and the counteracting anti-inflammatory response, remain a major health problem in worldwide. Emerging evidence suggests that methane have a protective effect on many animal models, like ischaemia reperfusion injury and diabetes-associated diseases. Whether methane could modulating inflammatory diseases remains largely unknown. Here we show that methane-rich saline (MS)iptreatment (16 ml/kg) alleviated endotoxin shock, bacteria-induced sepsis and dextran-sulfate-sodium-induced colitis in mice via decreased production of TNF-α and IL-6. In MS-treated macrophages, LPS-induced activation of NF-κb/MAPKs was attenuated. Interestingly, MS treatment significantly elevated the levels of IL-10 bothin vitroandin vivo. Neutralization of IL-10 abrogated the therapeutic effect of MS. Moreover, anti-IL10 blockade partially restored the MS-mediated attenuation of NF-κb/MAPKs phosphorylation. We further found that MS resulted in markedly enhanced phosphorylation of GSK-3β and AKT, which both mediate the release of Il-10. Additionally, inhibition of PI3K attenuated MS-mediated p-GSK-3β and IL-10 production and reversed the suppressed activation of NF-κb/ MAPKs in response to LPS. Our results reveal a novel effect and mechanisms of methane and support the potential value of MS as a therapeutic approach in innate inflammatory diseases.