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

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• 作者：Annika Nerstedt ; Emmelie Cansby ; Manoj Amrutkar ; Ulf Smith ; Margit Mahlapuu
• 关键词：AICAR ; 5-amino-4-imidazole-carboxamideriboside ; ACC ; acetyl-CoA carboxylase ; ALT ; alanine aminotransferase ; AMPK ; AMP-activated protein kinase ; CRP ; C-reactive protein ; HP ; haptoglobin ; IKK ; IkappaB kinase ; IL-6 ; Interleukin-6 ; IL6R¦Á ; IL-6 receptor subun
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2013
• 出版时间：15 August, 2013
• 年：2013
• 卷：375
• 期：1-2
• 页码：68-78
• 全文大小：684 K

文摘

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.