Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury.
Yue Hu,Jian Lou,Yuan-Yuan Mao,Tianwen Lai,Li-Yao Liu,Chen Zhu,Chao Zhang,Juan Liu,Yu-Yan Li,Fan Zhang,Wen Li,Songmin Ying,Zhihua Chen,Huahao Shen +13 more
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TLDR
Results demonstrate that activation of MTOR in the epithelium promotes LPS-induced ALI, likely through downregulation of autophagy and the subsequent activation of NFKB, and may represent a novel therapeutic strategy for preventing ALI induced by certain bacteria.Abstract:
MTOR (mechanistic target of rapamycin [serine/threonine kinase]) plays a crucial role in many major cellular processes including metabolism, proliferation and macroautophagy/autophagy induction, and is also implicated in a growing number of proliferative and metabolic diseases. Both MTOR and autophagy have been suggested to be involved in lung disorders, however, little is known about the role of MTOR and autophagy in pulmonary epithelium in the context of acute lung injury (ALI). In the present study, we observed that lipopolysaccharide (LPS) stimulation induced MTOR phosphorylation and decreased the expression of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β)-II, a hallmark of autophagy, in mouse lung epithelium and in human bronchial epithelial (HBE) cells. The activation of MTOR in HBE cells was mediated by TLR4 (toll-like receptor 4) signaling. Genetic knockdown of MTOR or overexpression of autophagy-related proteins significantly attenuated, whereas inhibition of autophagy ...read more
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Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles.
Lorenzo Galluzzi,Lorenzo Galluzzi,José Manuel Bravo-San Pedro,Beth Levine,Beth Levine,Douglas R. Green,Guido Kroemer +6 more
TL;DR: The therapeutic potential of autophagy modulators is discussed, the obstacles that have limited their development are analysed and strategies that may unlock the full therapeutic potential in the clinic are proposed.
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MicroRNA-377-3p released by mesenchymal stem cell exosomes ameliorates lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy
Xuxia Wei,Xiaomeng Yi,Haijin Lv,Xin Sui,Pinglan Lu,Lijuan Li,Yuling An,Yang Yang,Huimin Yi,Gui-hua Chen +9 more
TL;DR: In this paper, exosomes released by human mesenchymal stem cells (hucMSCs) were shown to regulate autophagy during acute lung injury and acute respiratory distress syndrome (ARDS).
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Complex interplay between autophagy and oxidative stress in the development of pulmonary disease.
Wojciech Ornatowski,Qing Lu,Manivannan Yegambaram,Alejandro E. Garcia,Evgeny A. Zemskov,Emin Maltepe,Jeffrey R. Fineman,Ting Wang,Stephen M. Black +8 more
TL;DR: This review highlights the current understanding on the interplay between ROS and autophagy in the development of pulmonary disease and suggests a central role for autophile as a mammalian oxidative stress response and its interrelationship to other stress defense systems.
Journal ArticleDOI
A COX-2/sEH dual inhibitor PTUPB alleviates lipopolysaccharide-induced acute lung injury in mice by inhibiting NLRP3 inflammasome activation.
Hui-Hui Yang,Jia-Xi Duan,Shao-Kun Liu,Jian-Bing Xiong,Xin-Xin Guan,Wen-Jing Zhong,Chen-Chen Sun,Chen-Yu Zhang,Xiao-Qin Luo,Yan-Feng Zhang,Ping Chen,Bruce D. Hammock,Sung Hee Hwang,Jian-Xin Jiang,Yong Zhou,Cha-Xiang Guan +15 more
TL;DR: The dual COX-2 and sEH inhibitor PTUPB exerts anti-inflammatory effects in treating ALI by inhibiting the NLRP3 inflammasome activation and improving the survival rate of mice receiving a lethal dose of LPS.
Journal ArticleDOI
Ammonia induces Treg/Th1 imbalance with triggered NF-κB pathway leading to chicken respiratory inflammation response.
TL;DR: Results are consistent with transcriptome detection, indicating that ammonia has a negative effect on immune responses and causes inflammatory injury of the trachea, and the molecular mechanism of NH3-PM2.5 induced respiratory diseases is explored.
References
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Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome
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