Send to

Choose Destination
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

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.


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.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center