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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

AMPK

IL-6

Inflammation

Liver

JAK1

protein-tyrosine-phosphatase

systemic insulin-resistance

c-reactive

protein

nf-kappa-b

skeletal-muscle

serine phosphorylation

metabolic

syndrome

kinase activation

endothelial-cells

5-aminoimidazole-4-carboxamide ribonucleoside

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