Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8477415 | Molecular and Cellular Endocrinology | 2013 | 11 Pages |
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.
Keywords
Sirt1gp130SOCS3sirtuin 1SAAIkappaB kinaseIRS-1IKKT2DJAK1PTPALTqRT-PCRSHPPTP1BLMO4STAT3NF-κBTCPTPACCAMPKAICARIL-6LPSJanus kinaseAMP-activated protein kinaseSmall interfering RNAsiRNAAlanine aminotransferaseacetyl-CoA carboxylaseinflammationinsulin receptor substrate-1interleukin-6tumour necrosis factor-αintraperitonealType 2 diabetesserum amyloid Asuppressor of cytokine signalling 3TNF-αnuclear factor-kappaBlipopolysaccharidesignal transducer and activator of transcription 3Haptoglobinquantitative real-time PCRT-cell protein tyrosine phosphataseProtein tyrosine phosphataseProtein tyrosine phosphatase 1BC-reactive proteinCRPJAKLiver
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Authors
Annika Nerstedt, Emmelie Cansby, Manoj Amrutkar, Ulf Smith, Margit Mahlapuu,