Production of interleukin-6 by skeletal myotubes: Role of reactive oxygen species

Ioanna Kosmidou, Theodoros Vassilakopoulos, Angeliki Xagorari, Spyros Zakynthinos, Andreas Papapetropoulos, Charis Roussos

Research output: Contribution to journalArticlepeer-review

157 Scopus citations


In the present study we have tested the ability of reactive oxygen species (ROS) to stimulate the production of interleukin (IL)-6 from skeletal myocytes. Differentiated C2C12 murine skeletal muscle cells (myotubes) exposed to pyrogallol (PYR), xanthine/xanthine-oxidase (X/XO), or H2O2 for 24 h exhibited a concentration-dependent increase in IL-6 production. Unlike myotubes, incubation of myoblasts and endothelial cells with X/XO or PYR did not result in increased IL-6 release. In myotubes, superoxide dismutase and catalase blocked the ROS-induced IL-6 release. Exposure of myotubes to H2O2 increased steady-state IL-6 mRNA levels, and pretreatment of myotubes with actinomycin D or cycloheximide abolished the ROS-induced IL-6 production. In addition, pretreatment of cells with N-acetyl-cysteine blocked tumor necrosis factor (TNF)-α-induced IL-6 release, suggesting that endogenously produced ROS participate in IL-6 production. Myotubes stimulated with H2O2 exhibited increased IκB-α phosphorylation and degradation, and treatment of C2C12 with ROS-generating agents increased activator protein (AP)-1 and nuclear factor (NF)-κB-dependent promoter activity. Finally, preincubation of myotubes with the pharmacologic inhibitor of NF-κB, diethyldithiocarbamate, or transient transfection with an IκB-α mutant, inhibited the ROS-stimulated IL-6 release. In conclusion, ROS stimulate IL-6 production from skeletal myotubes in a manner that involves transcriptional activation of the IL-6 gene through an NF-κB-dependent pathway.

Original languageEnglish (US)
Pages (from-to)587-593
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Issue number5
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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