A novel AMPK activator hernandezine inhibits LPS-induced TNFα production
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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
Xiaochuang Wang, email: [email protected]
Manxiang Li, email: [email protected]
Keywords: hernandezine, LPS, AMPK, TNFα, NFκB
Received: March 08, 2017 Accepted: May 03, 2017 Published: June 05, 2017
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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