Oncotarget

Research Papers:

miR-135b-5p inhibits LPS-induced TNFα production via silencing AMPK phosphatase Ppm1e

Ping Li, Jian-bo Fan, Yanxia Gao, Ming Zhang, Li Zhang, Ning Yang and Xiaojing Zhao _

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Oncotarget. 2016; 7:77978-77986. https://doi.org/10.18632/oncotarget.12866

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Abstract

Ping Li1, Jian-bo Fan2, Yanxia Gao1, Ming Zhang1, Li Zhang1, Ning Yang1, Xiaojing Zhao1

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

2Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong, China

Correspondence to:

Xiaojing Zhao, email: [email protected]

Keywords: miR-135b-5p, Ppm1e, AMPK, LPS, TNFα

Received: September 02, 2016    Accepted: October 05, 2016    Published: October 25, 2016

ABSTRACT

AMPK activation in monocytes could suppress lipopolysaccharide (LPS)-induced tissue-damaging TNFa production. We are set to provoke AMPK activation via microRNA (“miRNA”) downregulating its phosphatase Ppm1e. In human U937 and THP-1 monocytes, forced expression of microRNA-135b-5p (“miR-135b-5p”) downregulated Ppm1e and activated AMPK signaling. Further, LPS-induced TNFα production in above cells was dramatically attenuated. Ppm1e shRNA knockdown in U937 cells also activated AMPK and inhibited TNFα production by LPS. AMPK activation is required for miR-135b-induced actions in monocytes, AMPKα shRNA knockdown or T172A dominant negative mutation almost abolished miR-135b-5p’s suppression on LPS-induced TNFα production. Significantly, miR-135b-5p inhibited LPS-induced reactive oxygen species (ROS) production, NFκB activation and TNFα mRNA expression in human macrophages. AMPKα knockdown or mutation again abolished above actions by miR-135b-5p. We conclude that miR-135b-5p expression downregulates Ppm1e to activate AMPK signaling, which inhibits LPS-induced TNFα production via suppressing ROS production and NFκB activation.


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