机构：[a]Department of Medical Technology, Xi'an Medical University, China[b]Center of Stomatology, The Second Affiliated Hospital of Soochow University, Suzhou, China[c]Department of Emergency, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China
LPS stimulation in macrophages/monocytes induces TNF alpha production. We here tested the potential effect of GSK621, a novel AMP-activated protein kinase (AMPK) activator, against the process. In RAW264.7 macrophages, murine bone marrow-derived macrophages (BMDMs), and chronic obstructive pulmonary disease (COPD) patients' monocytes, GSK621 significantly inhibited LPS-induced TNFa protein secretion and mRNA synthesis. Inhibition of AMPK, through AMPK alpha shRNA knockdown or dominant negative mutation (T172A), almost abolished GSK621's suppression on TNF alpha in RAW264.7 cells. Reversely, forced expression of a constitutively-active AMPK alpha (T172D) mimicked GSK621 actions and reduced LPS-induced TNF alpha production. Molecularly, GSK621 suppressed LPS-induced reactive oxygen species (ROS) production and nuclear factor kappa B (NF kappa B) activation. In vivo, GSK621 oral administration inhibited LPS-induced TNF alpha production and endotoxin shock in mice. In summary, GSK621 activates AMPK signaling to inhibit LPS-induced TNF alpha production in macrophages/monocytes. (C) 2016 Elsevier Inc. All rights reserved.
基金：
This work is partly supported by the Science Foundation of
Jiangsu Province and NSFC.
第一作者机构：[a]Department of Medical Technology, Xi'an Medical University, China
共同第一作者：
通讯作者：
通讯机构：[a]Department of Medical Technology, Xi'an Medical University, China[c]Department of Emergency, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China
推荐引用方式(GB/T 7714)：
Yong-hong Wu,Quan Li,Ping Li,et al.GSK621 activates AMPK signaling to inhibit LPS-induced TNF alpha production[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2016,480(3):289-295.doi:10.1016/j.bbrc.2016.10.001.
APA：
Yong-hong Wu,Quan Li,Ping Li&Bei Liu.(2016).GSK621 activates AMPK signaling to inhibit LPS-induced TNF alpha production.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,480,(3)
MLA：
Yong-hong Wu,et al."GSK621 activates AMPK signaling to inhibit LPS-induced TNF alpha production".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 480..3(2016):289-295
