Epithelial Cells Attenuate Toll-Like Receptor-Mediated Inflammatory Responses in Monocyte-Derived Macrophage-Like Cells to Mycobacterium tuberculosis by Modulating the PI3K/Akt/mTOR Signaling Pathway.
Epithelial Cells Attenuate Toll-Like Receptor-Mediated Inflammatory Responses in Monocyte-Derived Macrophage-Like Cells to Mycobacterium tuberculosis by Modulating the PI3K/Akt/mTOR Signaling Pathway.
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上皮细胞通过调节 PI3K/Akt/mTOR 信号通路减弱单核细胞衍生的巨噬细胞样细胞对结核分枝杆菌的 Toll 样受体介导的炎症反应
DOI：
10.1155/2018/3685948
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发表时间：
2018
影响因子：
4.6
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Yang Y;Sun Y;Xu J;Bao K;Luo M;Liu X;Wang Y
肺泡巨噬细胞（AM）和肺泡上皮细胞（AEC）是结核分枝杆菌（M.结核病（Mtb））。粘膜AEC和AM之间的细胞间通讯在细胞对外源性损伤的反应中具有重要意义。然而，支持对Mtb的相互作用的分子机制在很大程度上仍然未知。在这项研究中，AECs对Toll样受体（TLR-）介导的AM对Mtb强毒株H37 Rv的炎症反应的影响，使用上皮A549细胞和U937单核细胞衍生的巨噬细胞样细胞的气液界面（ALI）共培养模型进行了调查。结果表明，与单独感染U937细胞相比，当A549细胞与H37 Rv共感染时，U937细胞中Mtb激活的TLR介导的炎症反应显著减轻。在机制上，PI 3 K/Akt/mTOR信号通路参与上皮细胞调节的Mtb激活的TLR信号通路。U937 s中上皮细胞减弱的TLR信号可以被PI 3 K抑制剂LY 294002和mTOR抑制剂雷帕霉素逆转，但不能被糖原合成酶激酶3β抑制剂LiCl逆转，表明巨噬细胞中上皮细胞调节的TLR信号部分是通过抑制TLR触发的PI 3 K/Akt/mTOR信号通路引起的。总之，这项研究表明，粘膜AEC衍生的信号在调节AM对Mtb的炎症反应中起着重要作用，因此也提供了对AEC和AM之间对Mtb感染的细胞通信的见解。
Both alveolar macrophages (AMs) and alveolar epithelial cells (AECs) are main targets of Mycobacterium tuberculosis (M. tuberculosis (Mtb)). Intercellular communications between mucosal AECs and AMs have important implications in cellular responses to exogenous insults. However, molecular mechanisms underpinning interactions responding to Mtb remain largely unknown. In this study, impacts of AECs on Toll-like receptor- (TLR-) mediated inflammatory responses of AMs to Mtb virulent strain H37Rv were interrogated using an air-liquid interface (ALI) coculture model of epithelial A549 cells and U937 monocyte-derived macrophage-like cells. Results showed that Mtb-activated TLR-mediated inflammatory responses in U937 cells were significantly alleviated when A549 cells were coinfected with H37Rv, in comparison with the infection of U937 cells alone. Mechanistically, PI3K/Akt/mTOR signaling was involved in the epithelial cell-modulated Mtb-activated TLR signaling. The epithelial cell-attenuated TLR signaling in U937s could be reversed by PI3K inhibitor LY294002 and mTOR inhibitor rapamycin, but not glycogen synthase kinase 3β inhibitor LiCl, suggesting that the epithelially modulated-TLR signaling in macrophages was in part caused by inhibiting the TLR-triggered PI3K/Akt/mTOR signaling pathway. Together, this study demonstrates that mucosal AEC-derived signals play an important role in modulating inflammatory responses of AMs to Mtb, which thus also offers an insight into cellular communications between AECs and AMs to Mtb infections.
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影响因子：
4.8
作者：
Huang, Guochang;Redelman-Sidi, Gil;Jiang, Xuejun
通讯作者：
Jiang, Xuejun
影响因子：
3.6
作者：
Ma, Yan;Han, Fei;Liu, Xiaoming
通讯作者：
Liu, Xiaoming
影响因子：
9.3
作者：
Beurel E;Jope RS
通讯作者：
Jope RS
DOI：
10.1165/rcmb.2003-0091oc
发表时间：
2004-03-01
影响因子：
6.4
作者：
Atochina, EN;Beers, MF;Gow, AJ
通讯作者：
Gow, AJ
影响因子：
3.1
作者：
Honko, AN;Mizel, SB
通讯作者：
Mizel, SB