title: Pharmacological activation of AMPK suppresses inflammatory response evoked by IL-6 signalling in mouse liver and in human hepatocytes.
abstract: Interleukin-6 (IL-6) induces inflammatory signalling in liver, leading to impaired insulin action in hepatocytes. In this study, we demonstrate that pharmacological activation of AMP-activated protein kinase (AMPK) represses IL-6-stimulated expression of proinflammatory markers serum amyloid A (Saa) as well as suppressor of cytokine signalling 3 (Socs3) in mouse liver. Further studies using the human hepatocellular carcinoma cell line HepG2 suggest that AMPK inhibits IL-6 signalling by repressing IL-6-stimulated phosphorylation of several downstream components of the pathway such as Janus kinase 1 (JAK1), SH2-domain containing protein tyrosine phosphatase 2 (SHP2) and signal transducer and activator of transcription 3 (STAT3). In summary, inhibition of IL-6 signalling cascade in liver by the metabolic master switch of the body, AMPK, supports the role of this kinase as a crucial point of convergence of metabolic and inflammatory pathways in hepatocytes.
authors.affiliation: The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, University of Gothenburg, SE-413 45 Gothenburg, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Nerstedt
authors.forename: Emmelie
authors.initials: E
authors.lastname: Cansby
authors.forename: Manoj
authors.initials: M
authors.lastname: Amrutkar
authors.forename: Ulf
authors.initials: U
authors.lastname: Smith
authors.forename: Margit
authors.initials: M
authors.lastname: Mahlapuu
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012265:Ribonucleotides / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D020536:Enzyme Activators; C508600:IL6 protein, human; D015850:Interleukin-6; D012265:Ribonucleotides; D050796:STAT3 Transcription Factor; C489995:Saa2 protein, mouse; D000685:Serum Amyloid A Protein; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000620:Aminoimidazole Carboxamide; D008687:Metformin; D000263:Adenylate Kinase; C031143:AICA ribonucleotide