Nitric oxide stimulates interleukin-6 production in skeletal myotubes

Anastasia C. Makris, Yannis Sotzios, Zongmin Zhou, Maria Makropoulou, Nektarios Papapetropoulos, Panagiotis Zacharatos, Anastasia Pyriochou, Charis Roussos, Andreas Papapetropoulos, Theodoros Vassilakopoulos

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Strenuous exercise leads to the up-regulation of interleukin-6 (IL-6) production and enhanced nitric oxide (NO) release within the contracting skeletal muscles. In this study, we investigated whether NO regulates IL-6 production in C2C12 myotubes. These cells exhibited a concentration-dependent increase in IL-6 production upon stimulation with NO donors (Z)-1-[N-(2- aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate), (Z)-1-[N-(3-aminopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA-NONOate), and sodium nitroprusside (SNP). This treatment did not alter cGMP levels nor did the soluble guanylyl cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one(ODQ), alter this response. The NO-independent sGC activator 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3, 4-b]pyridin-3-yl]-pyrimidin-4-ylamine (BAY41-2272) and cyclic guanosine monophosphate (cGMP) analog 8Br-cGMP failed to induce IL-6 production. Upon exposure to NO donors, we observed an increase in Erk1/2 and p38 MAPK phosphorylation but not in SAPK/JNK. In addition, NO-induced IL-6 release was inhibited in a concentration-dependent fashion by the MEK1/2 inhibitor PD98059 and the p38 MAPK inhibitor SB203580 but not by the SAPK/JNK inhibitor SP600125. We conclude that NO-stimulated IL-6 production in differentiated C2C12 myotubes is cGMP-independent and mediated by activation of MAPK pathways.

Original languageEnglish (US)
Pages (from-to)321-327
Number of pages7
JournalJournal of Interferon and Cytokine Research
Issue number5
StatePublished - May 1 2010
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology


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