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 journalArticle

11 Citations (Scopus)

Abstract

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
Volume30
Issue number5
DOIs
StatePublished - May 1 2010
Externally publishedYes

Fingerprint

Skeletal Muscle Fibers
Interleukin-6
Nitric Oxide
Cyclic GMP
Nitric Oxide Donors
p38 Mitogen-Activated Protein Kinases
Nitroprusside
Skeletal Muscle
Up-Regulation
Phosphorylation

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

Cite this

Makris, A. C., Sotzios, Y., Zhou, Z., Makropoulou, M., Papapetropoulos, N., Zacharatos, P., ... Vassilakopoulos, T. (2010). Nitric oxide stimulates interleukin-6 production in skeletal myotubes. Journal of Interferon and Cytokine Research, 30(5), 321-327. https://doi.org/10.1089/jir.2009.0022

Nitric oxide stimulates interleukin-6 production in skeletal myotubes. / Makris, Anastasia C.; Sotzios, Yannis; Zhou, Zongmin; Makropoulou, Maria; Papapetropoulos, Nektarios; Zacharatos, Panagiotis; Pyriochou, Anastasia; Roussos, Charis; Papapetropoulos, Andreas; Vassilakopoulos, Theodoros.

In: Journal of Interferon and Cytokine Research, Vol. 30, No. 5, 01.05.2010, p. 321-327.

Research output: Contribution to journalArticle

Makris, AC, Sotzios, Y, Zhou, Z, Makropoulou, M, Papapetropoulos, N, Zacharatos, P, Pyriochou, A, Roussos, C, Papapetropoulos, A & Vassilakopoulos, T 2010, 'Nitric oxide stimulates interleukin-6 production in skeletal myotubes', Journal of Interferon and Cytokine Research, vol. 30, no. 5, pp. 321-327. https://doi.org/10.1089/jir.2009.0022
Makris AC, Sotzios Y, Zhou Z, Makropoulou M, Papapetropoulos N, Zacharatos P et al. Nitric oxide stimulates interleukin-6 production in skeletal myotubes. Journal of Interferon and Cytokine Research. 2010 May 1;30(5):321-327. https://doi.org/10.1089/jir.2009.0022
Makris, Anastasia C. ; Sotzios, Yannis ; Zhou, Zongmin ; Makropoulou, Maria ; Papapetropoulos, Nektarios ; Zacharatos, Panagiotis ; Pyriochou, Anastasia ; Roussos, Charis ; Papapetropoulos, Andreas ; Vassilakopoulos, Theodoros. / Nitric oxide stimulates interleukin-6 production in skeletal myotubes. In: Journal of Interferon and Cytokine Research. 2010 ; Vol. 30, No. 5. pp. 321-327.
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