Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKβ/NF-κB signaling.
Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKβ/NF-κB signaling.
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DOI：
10.1371/journal.pone.0017598
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发表时间：
2011-03-08
期刊：
影响因子：
3.7
通讯作者：
Lin CF
中科院分区：
文献类型：
--
作者：
Hsing CH;Lin MC;Choi PC;Huang WC;Kai JI;Tsai CC;Cheng YL;Hsieh CY;Wang CY;Chang YP;Chen YH;Chen CL;Lin CF
麻醉异丙酚具有免疫调节作用，特别是在抗炎症方面。细菌内毒素脂多糖（LPS）通过toll样受体（TLR） 4信号传导诱导炎症。我们研究了异丙酚对LPS/ tlr4诱导的小鼠RAW264.7巨噬细胞炎症激活的分子作用。通过western blotting和Griess反应测定，异丙酚的非细胞毒性水平分别降低了lps诱导的诱导型一氧化氮合酶（iNOS）和一氧化氮（NO）。通过酶联免疫吸附法检测，异丙酚还能降低肿瘤坏死因子-α (TNF-α)、白细胞介素(IL)-6和IL-10的产生。Western blot分析显示，异丙酚抑制lps诱导的IKKβ (Ser180)和NF -κB （Ser536）的活化和磷酸化；随后NF-κB p65的核易位也减少。此外，异丙酚通过减少活性氧（ROS）的产生，抑制lps诱导的Akt活化和磷酸化（Ser473）；研究发现，ROS调控Akt后NF-κB活化对巨噬细胞lps诱导的炎症反应至关重要。C57BL/6小鼠的体内研究也显示了对腹腔巨噬细胞LPS的抗炎作用。这些结果表明，异丙酚通过抑制相互关联的ROS/Akt/IKKβ/NF-κB信号通路来降低巨噬细胞lps诱导的炎症反应。
Anesthetic propofol has immunomodulatory effects, particularly in the area of anti-inflammation. Bacterial endotoxin lipopolysaccharide (LPS) induces inflammation through toll-like receptor (TLR) 4 signaling. We investigated the molecular actions of propofol against LPS/TLR4-induced inflammatory activation in murine RAW264.7 macrophages. Non-cytotoxic levels of propofol reduced LPS-induced inducible nitric oxide synthase (iNOS) and NO as determined by western blotting and the Griess reaction, respectively. Propofol also reduced the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 as detected by enzyme-linked immunosorbent assays. Western blot analysis showed propofol inhibited LPS-induced activation and phosphorylation of IKKβ (Ser180) and nuclear factor (NF)-κB (Ser536); the subsequent nuclear translocation of NF-κB p65 was also reduced. Additionally, propofol inhibited LPS-induced Akt activation and phosphorylation (Ser473) partly by reducing reactive oxygen species (ROS) generation; inter-regulation that ROS regulated Akt followed by NF-κB activation was found to be crucial for LPS-induced inflammatory responses in macrophages. An in vivo study using C57BL/6 mice also demonstrated the anti-inflammatory properties against LPS in peritoneal macrophages. These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways.
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DOI：
10.1097/shk.0b013e318180f508
发表时间：
2009-01
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Nomellini V;Gomez CR;Gamelli RL;Kovacs EJ
通讯作者：
Kovacs EJ
影响因子：
5
作者：
Jang, Seon;Kim, Hyung Jin;You, Yong-Ouk
通讯作者：
You, Yong-Ouk
影响因子：
5.1
作者：
Chiu, Wen-Ta;Lin, Yi-Ling;Chen, Ruei-Ming
通讯作者：
Chen, Ruei-Ming
影响因子：
4.8
作者：
Sanlioglu, S;Williams, CM;Engelhardt, JF
通讯作者：
Engelhardt, JF
影响因子：
4.1
作者：
Marik, PE
通讯作者：
Marik, PE