Pharmacological activation of AMPK suppresses inflammatory response evoked by IL-6 signalling in mouse liver and in human hepatocytes

Nerstedt, Annika,1960Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine (author)

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.

Cansby, Emmelie,1984Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xcanem (author)
Amrutkar, ManojGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine (author)
Smith, Ulf,1943Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xsmiul (author)
Mahlapuu, Margit,1972Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xmahma (author)
Göteborgs universitetInstitutionen för medicin, avdelningen för molekylär och klinisk medicin (creator_code:org_t)

By the author/editor: Nerstedt, Annika ...; Cansby, Emmelie, ...; Amrutkar, Manoj; Smith, Ulf, 1943; Mahlapuu, Margit ...

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