title: miR-135b-5p inhibits LPS-induced TNFα production via silencing AMPK phosphatase Ppm1e.
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.
authors: Department of Emergency, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China.
authors: Ping
authors: P
authors: Li
authors: Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong, China.
authors: Jian-Bo
authors: JB
authors: Fan
authors: Department of Emergency, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China.
authors: Yanxia
authors: Y
authors: Gao
authors: Department of Emergency, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China.
authors: Ming
authors: M
authors: Zhang
authors: Department of Emergency, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China.
authors: Li
authors: L
authors: Zhang
authors: Department of Emergency, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China.
authors: Ning
authors: N
authors: Yang
authors: Department of Emergency, The Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China.
authors: Xiaojing
authors: X
authors: Zhao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D000071636:Protein Phosphatase 2C / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism; D020298:U937 Cells
chemical_list: D008070:Lipopolysaccharides; C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D055372:AMP-Activated Protein Kinases; C000607459:PPM1E protein, human; D000071636:Protein Phosphatase 2C
keywords: AMPK; LPS; Ppm1e; TNFα; miR-135b-5p