Glucagon counteracts interleukin-6-dependent gene expression by redundant action of Epac and PKA
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Christina Khouri
Abstract
Inflammation is the biological response to injurious stimuli. In the initial phase of the inflammatory process, interleukin-6 (IL-6) is the main inducer of acute phase protein expression in the liver. A prolonged acute phase response is characterised by a disturbed glucose homeostasis and elevated levels of IL-6, insulin, and counterregulatory hormones such as glucagon. Several studies deal with the impact of IL-6 on glucagon-dependent gene expression. In contrast, only very little is known about the influence of G-protein-coupled receptors on IL-6 signalling. Therefore, the aim of this study is to elucidate the regulation of IL-6-induced gene expression by glucagon. We could reveal a novel mechanism of negative regulation of IL-6-induced MAP kinase activation by glucagon in primary murine hepatocytes. IL-6-dependent induction of the ERK-dependent target gene Tfpi2, coding for a Kunitz-type serine protease inhibitor, was strongly down-regulated by glucagon treatment. Studying the underlying mechanism revealed a redundant action of the signalling molecules exchange protein activated by cyclic AMP (Epac) and protein kinase A. The metabolic hormone glucagon interferes in IL-6-induced gene expression. This observation is indicative for a regulatory role of G-protein-coupled receptors in the IL-6-dependent inflammatory response.
©2011 by Walter de Gruyter Berlin Boston
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Articles in the same Issue
- Reviews
- Squalene monooxygenase – a target for hypercholesterolemic therapy
- Cysteine proteinase SpeB from Streptococcus pyogenes – a potent modifier of immunologically important host and bacterial proteins
- Protein Structure and Function
- S-Glucuronidation of 7-mercapto-4-methylcoumarin by human UDP glycosyltransferases in genetically engineered fission yeast cells
- Dimerization of human 5-lipoxygenase
- Cloning, expression, characterization and inhibition studies on trypanothione synthetase, a drug target enzyme, from Leishmania donovani
- Cell Biology and Signaling
- Glucagon counteracts interleukin-6-dependent gene expression by redundant action of Epac and PKA
- The influenza virus PB1-F2 protein has interferon antagonistic activity
- Somatotropic gene response to recombinant growth hormone treatment in buffalo leucocytes
- Ammonia increases nitric oxide, free Zn2+, and metallothionein mRNA expression in cultured rat astrocytes
- Proteolysis
- Expression pattern of cathepsin W isoforms in peripheral blood and gastroesophageal mucosa of patients with gastroesophageal reflux disease
