Oncotarget

Research Papers:

A novel AMPK activator hernandezine inhibits LPS-induced TNFα production

Ping Li, Xiaofang Li, Yonghong Wu, Manxiang Li and Xiaochuang Wang _

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Oncotarget. 2017; 8:67218-67226. https://doi.org/10.18632/oncotarget.18365

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Abstract

Ping Li1,*, Xiaofang Li2,*, Yonghong Wu3, Manxiang Li4 and Xiaochuang Wang5

1Department of Emergency, The Second Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, China

2Department of Gastroenterology, The Third People’s Hospital of Xi’an, Xi’an, China

3Staff Room of Clinical Immunology and Pathogen Detection, Medical Technology Department, Xi’an Medical College, Xi’an, China

4Department of Respiratory Medicine, The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, China

5Department of Critical Care Medicine, The Second Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, China

*These authors have contributed equally to this work

Correspondence to:

Xiaochuang Wang, email: wangxiaochuangyshi@126.com

Manxiang Li, email: drli_manxiang88@163.com

Keywords: hernandezine, LPS, AMPK, TNFα, NFκB

Received: March 08, 2017    Accepted: May 03, 2017    Published: June 05, 2017

ABSTRACT

Here, we found that hernandezine, a novel AMPK activator, inhibited LPS-induced TNFα expression/production in human macrophage cells (THP-1 and U937 lines). Activation of AMPK is required for hernandezine-induced anti-LPS response. AMPKα shRNA or dominant negative mutation (T172A) blocked hernandezine-induced AMPK activation, which almost completely reversed anti-LPS activity by hernandezine. Exogenous expression of the constitutively activate AMPKα (T172D, caAMPKα) also suppressed TNFα production by LPS. Remarkably, hernandezine was unable to further inhibit LPS-mediated TNFα production in caAMPKα-expressing cells. Hernandezine inhibited LPS-induced reactive oxygen species (ROS) production and nuclear factor kappa B (NFκB) activation. Treatment of hernandezine in ex-vivo cultured primary human peripheral blood mononuclear cells (PBMCs) also largely attenuated LPS-induced TNFα production. Together, we conclude that AMPK activation by hernandezine inhibits LPS-induced TNFα production in macrophages/monocytes.


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