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Cytokine. 2006 Nov;36(3-4):141-7. Epub 2007 Jan 2.

Differential regulation of IL-6 and TNF-alpha via calcineurin in human skeletal muscle cells.

Author information

1
Centre of Inflammation and Metabolism, Department of Infectious Diseases and the Copenhagen Muscle Research Centre, Faculty of Health Sciences, University Hospital of Copenhagen, Tagensvej 20, 2200 Copenhagen N, Denmark. ckeller@inflammation-metabolism.dk

Abstract

Interleukin-6 increases in skeletal muscle during exercise, and evidence points to Ca2+ as an initiator of IL-6 production. However, the signalling pathway whereby this occurs is unknown. One candidate for Ca2+ -mediated IL-6 induction is calcineurin, an activator of NF-AT. Here we investigated whether skeletal myocytes produce IL-6 in a Ca2+/calcineurin-dependent manner, and whether TNF-alpha, an inducer of IL-6, is affected by these stimuli. Human skeletal muscle cell cultures were stimulated with ionomycin time-and dose-dependently to elevate intracellular Ca2+ levels, with or without addition of cyclosporin A (CSA); a calcineurin inhibitor. mRNA was extracted from myocytes and analysed for IL-6 and TNF-alpha gene expression. IL-6 mRNA increased time- and dose-dependently with ionomycin stimulation, an effect that was blunted by approximately 75% in the presence of CSA. In contrast, TNF-alpha gene expression was decreased by approximately 70% in response to ionomycin treatment, but increased in response to addition of CSA. These data demonstrate that IL-6 and TNF-alpha are regulated differentially in skeletal muscle cells in response to a Ca2+ stimulus. Blocking the calcineurin pathway resulted in inhibition of the IL-6 response to ionomycin, whereas TNF-alpha increased by addition of CSA, further indicating a differential regulation of IL-6 and TNF-alpha in human skeletal myocytes.

PMID:
17197194
DOI:
10.1016/j.cyto.2006.10.014
[Indexed for MEDLINE]

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