Inhibition of autophagy with 3-methyladenine is protective in a lethal model of murine endotoxemia and polymicrobial sepsis.
Inhibition of autophagy with 3-methyladenine is protective in a lethal model of murine endotoxemia and polymicrobial sepsis.
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3-甲基腺嘌呤抑制自噬在小鼠内毒素血症和多种微生物败血症的致死模型中具有保护作用
DOI：
10.1177/1753425918771170
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发表时间：
2018-05
期刊：
影响因子：
3.2
通讯作者：
Fang M
中科院分区：
文献类型：
--
作者：
Li Q;Li L;Fei X;Zhang Y;Qi C;Hua S;Gong F;Fang M
在此，在LPS诱导的致死性内毒素休克小鼠模型和盲肠结扎穿孔（CLP）小鼠模型中检查自噬的调节作用。自噬抑制剂3-甲基腺嘌呤（3-MA）和自噬增强剂雷帕霉素被给予LPS或CLP攻击的小鼠。LPS或CLP联合3-MA攻击的动物在内毒素血症后显示出存活率增加，但LPS联合雷帕霉素加重了小鼠的内毒素休克。在所研究的不同器官中，肺和肠在单独LPS、LPS与3-MA组合和LPS与雷帕霉素组合之间表现出显著差异。LPS与3-MA联合应用可减轻上述器官的炎性损伤。与此相反，LPS与雷帕霉素结合增加了这些器官的损伤。结论：LPS联合3-MA可降低血清TNF-α和IL-6水平，而LPS联合雷帕霉素可升高血清TNF-α和IL-6水平。在暴露于LPS的小鼠骨髓源性巨噬细胞中发现了类似的结果。此外，自噬对内毒素休克的调节作用依赖于TLR 4信号通路。我们的研究结果表明，自噬在内毒素休克的调节和内毒素休克治疗的潜在调制的核心作用。
Here, the regulatory role of autophagy is examined in both an LPS-induced lethal endotoxic shock mouse model and cecal ligation and puncture (CLP) mouse model. Autophagy-inhibitor 3-methyladenine (3-MA) and autophagy-enhancer rapamycin were administrated to mice challenged with LPS or CLP. Animals challenged with LPS or CLP combined with 3-MA displayed increased survival after endotoxemia, but LPS combined with rapamycin worsened the endotoxic shock of the mice. Among the different organs studied, the lungs and intestines exhibited significant differences among LPS alone, LPS combined with 3-MA and LPS combined with rapamycin. LPS combined with 3-MA attenuated the inflammatory damages of these organs as compared with LPS alone. In contrast, LPS combined with rapamycin increased damage in these organs. Consistently, serum inflammatory mediators TNF-α and IL-6 were decreased by the treatment of LPS combined with 3-MA as compared with LPS alone, while administration of LPS combined with rapamycin increased the serum TNF-α and IL-6 levels. Similar results were found in mouse bone marrow-derived macrophages exposed to LPS. Moreover, the regulatory effect of autophagy to endotoxic shock is dependent on the TLR4 signaling pathway. Our results demonstrate the central role of autophagy in the regulation of endotoxic shock and its potential modulation for endotoxic shock treatment.
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影响因子：
3.7
作者：
Wang LT;Chen BL;Wu CT;Huang KH;Chiang CK;Hwa Liu S
通讯作者：
Hwa Liu S
DOI：
10.1007/s00109-016-1502-4
发表时间：
2017-05
期刊：
Journal of molecular medicine (Berlin, Germany)
影响因子：
--
作者：
Liu H;Smith AJ;Ball SS;Bao Y;Bowater RP;Wang N;Michael Wormstone I
通讯作者：
Michael Wormstone I
影响因子：
13.3
作者：
Giegerich, Annika Klara;Kuchler, Laura;von Knethen, Andreas
通讯作者：
von Knethen, Andreas
甘草酸通过调节抗原呈递细胞来减弱产生白细胞介素 17 的 T 细胞反应，从而改善实验性结肠炎
影响因子：
4.4
作者：
Chen, Xiangyu;Fang, Dai;Fang, Min
通讯作者：
Fang, Min
影响因子：
14
作者：
Kim, Ye-Ram;Koh, Hyun-Jung;Yang, Chul-Su
通讯作者：
Yang, Chul-Su