Propofol suppresses microglial phagocytosis through the downregulation of MFG-E8.
Propofol suppresses microglial phagocytosis through the downregulation of MFG-E8.
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DOI：
10.1186/s12974-020-02061-3
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发表时间：
2021-01-09
影响因子：
9.3
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Cai X;Li Y;Zheng X;Hu R;Li Y;Xiao L;Wang Z
小胶质细胞是健康大脑中高度活动的吞噬细胞，具有监视和清除功能。尽管小胶质细胞已被证明可以在脑损伤后吞噬细胞碎片，但人们对它们在没有损伤的情况下的吞噬功能知之甚少。异丙酚可以抑制小胶质细胞的活性，包括吞噬作用。乳脂球表皮生长因子 8 (MFG-E8) 作为小胶质细胞的调节剂，在吞噬过程中发挥着重要作用。然而，MFG-E8是否影响异丙酚吞噬作用的改变仍不清楚。小胶质细胞 BV2 细胞用异丙酚处理，有或没有 MFG-E8。通过流式细胞术和免疫荧光评估乳胶珠的吞噬作用。通过蛋白质印迹分析评估 MFG-E8、p-AMPK、AMPK、p-Src 和 Src 水平。应用化合物C（AMPK抑制剂）和达沙替尼（Src抑制剂）测定丙泊酚治疗下AMPK和Src在小胶质细胞吞噬作用中的作用。异丙酚处理4 h后小胶质细胞吞噬能力显着下降（P < 0.05）。异丙酚以浓度和时间依赖性方式抑制 MFG-E8 的产生（P < 0.05）。预先给予 MFG-E8 剂量依赖性（从 10 至 100ng/ml）可逆转丙泊酚对吞噬作用的抑制（P < 0.05）。此外，MFG-E8 激活逆转了丙泊酚干预引起的 p-AMPK 和 p-Src 水平下降（P < 0.05）。给予小胶质细胞化合物C（AMPK抑制剂）和达沙替尼（Src抑制剂）可阻断MFG-E8诱导的吞噬作用增强的趋势（P < 0.05）。这些发现揭示了 MFG-E8 在丙泊酚和小胶质细胞吞噬活性之间的中间作用。此外，MFG-E8 可能通过调节 AMPK 和 Src 信号通路来逆转丙泊酚诱导的吞噬作用的抑制。
Microglia are highly motile phagocytic cells in the healthy brain with surveillance and clearance functions. Although microglia have been shown to engulf cellular debris following brain insult, less is known about their phagocytic function in the absence of injury. Propofol can inhibit microglial activity, including phagocytosis. Milk fat globule epidermal growth factor 8 (MFG-E8), as a regulator of microglia, plays an essential role in the phagocytic process. However, whether MFG-E8 affects the alteration of phagocytosis by propofol remains unknown. Microglial BV2 cells were treated with propofol, with or without MFG-E8. Phagocytosis of latex beads was evaluated by flow cytometry and immunofluorescence. MFG-E8, p-AMPK, AMPK, p-Src, and Src levels were assessed by western blot analysis. Compound C (AMPK inhibitor) and dasatinib (Src inhibitor) were applied to determine the roles of AMPK and Src in microglial phagocytosis under propofol treatment. The phagocytic ability of microglia was significantly decreased after propofol treatment for 4 h (P < 0.05). MFG-E8 production was inhibited by propofol in a concentration- and time-dependent manner (P < 0.05). Preadministration of MFG-E8 dose-dependently (from 10 to 100 ng/ml) reversed the suppression of phagocytosis by propofol (P < 0.05). Furthermore, the decline in p-AMPK and p-Src levels induced by propofol intervention was reversed by MFG-E8 activation (P < 0.05). Administration of compound C (AMPK inhibitor) and dasatinib (Src inhibitor) to microglia blocked the trend of enhanced phagocytosis induced by MFG-E8 (P < 0.05). These findings reveal the intermediate role of MFG-E8 between propofol and microglial phagocytic activity. Moreover, MFG-E8 may reverse the suppression of phagocytosis induced by propofol through the regulation of the AMPK and Src signaling pathways.
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影响因子：
5.3
作者：
Fernández-Arjona MDM;Grondona JM;Granados-Durán P;Fernández-Llebrez P;López-Ávalos MD
通讯作者：
López-Ávalos MD
影响因子：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
影响因子：
34.7
作者：
Brown, Guy C.;Neher, Jonas J.
通讯作者：
Neher, Jonas J.
影响因子：
4
作者：
Raymond, Adam;Ensslin, Michael A.;Shur, Barry D.
通讯作者：
Shur, Barry D.
DOI：
10.1186/s10020-018-0054-1
发表时间：
2018-11-23
期刊：
Molecular medicine (Cambridge, Mass.)
影响因子：
--
作者：
Sun B;Ou H;Ren F;Huan Y;Zhong T;Gao M;Cai H
通讯作者：
Cai H