© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Induction of iNOS expression in skeletal muscle by IL-1β and NF
B activation: an in vitro and in vivo study
University Leipzig–Heart Center Leipzig, Clinic of Cardiology, Leipzig, Germany
* Corresponding author. Universität Leipzig, Herzzentrum GmbH, Klinik für Innere Medizin/Kardiologie, Strümpellstrasse 39, D-04289 Leipzig, Germany. Tel.: +49-341-865-1620; fax: +49-341-865-1461 adav{at}medizin.uni-leipzig.de
Objective: The intracellular pathway and the regulation of inducible nitric oxide synthase (iNOS) expression in skeletal muscle is incompletely understood. In vitro studies, using different cell types, suggest that inflammatory cytokines are potential triggers to induce iNOS expression. Methods: To analyze intracellular pathways leading to iNOS induction, rat skeletal myoblasts were incubated with inflammatory cytokines and assessed for iNOS expression by Western blot and Griess reaction. To confirm the in vitro findings, local cytokine levels were determined in skeletal muscle biopsies of patients with chronic heart failure (CHF) and correlated with iNOS expression. Results: Nitrite accumulation in the myoblast culture supernatant or iNOS protein in the cell pellet was significantly increased after incubation with IL-1β in combination with 
-IFN. Priming experiments revealed that -IFN elevated the expression of IL-1β receptor mRNA, whereby IL-1β was able to induce iNOS expression. The cytokine-mediated iNOS induction was significantly reduced by blocking ERK1/ERK2 activation and completely abolished by the inhibition of NF
B. In skeletal muscle biopsies of CHF patients the local content of IL-1β was significantly increased as compared to healthy controls. Furthermore, a linear correlation between IL-1β content and iNOS expression in the skeletal muscle was detected. Conclusions: These data demonstrate that IL-1β, together with the priming effect of -IFN, induces iNOS expression in skeletal muscle via activation of ERK1/ERK2 and NFB.
KEYWORDS Heart failure; Nitric oxide; Cytokines; Signal transduction
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Katada, A. Bihari, A. Badhwar, N. Yoshida, T. Yoshikawa, R. F. Potter, and G. Cepinskas Hindlimb Ischemia/Reperfusion-Induced Remote Injury to the Small Intestine: Role of Inducible Nitric-Oxide Synthase-Derived Nitric Oxide J. Pharmacol. Exp. Ther., June 1, 2009; 329(3): 919 - 927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Song, H.-B. Kwak, J.-H. Kim, and J. M. Lawler Exercise Training Modulates the Nitric Oxide Synthase Profile in Skeletal Muscle From Old Rats J Gerontol A Biol Sci Med Sci, May 1, 2009; 64A(5): 540 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Schmidt, K. Barthel, A. Wrede, M. Salajegheh, M. Bahr, and M. C. Dalakas Interrelation of inflammation and APP in sIBM: IL-1{beta} induces accumulation of {beta}-amyloid in skeletal muscle Brain, May 1, 2008; 131(5): 1228 - 1240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Lawler, H.-B. Kwak, W. Song, and J. L. Parker Exercise training reverses downregulation of HSP70 and antioxidant enzymes in porcine skeletal muscle after chronic coronary artery occlusion Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1756 - R1763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nimata, T.-a. Okabe, M. Hattori, Z. Yuan, K. Shioji, and C. Kishimoto MCI-186 (edaravone), a novel free radical scavenger, protects against acute autoimmune myocarditis in rats Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2514 - H2518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Jankowska, S. von Haehling, A. Czarny, E. Zaczynska, A. Kus, S. D. Anker, W. Banasiak, and P. Ponikowski Activation of the NF-{kappa}B system in peripheral blood leukocytes from patients with chronic heart failure Eur J Heart Fail, October 1, 2005; 7(6): 984 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Chevrel, C Granet, and P Miossec Contribution of tumour necrosis factor {alpha} and interleukin (IL) 1{beta} to IL6 production, NF-{kappa}B nuclear translocation, and class I MHC expression in muscle cells: in vitro regulation with specific cytokine inhibitors Ann Rheum Dis, September 1, 2005; 64(9): 1257 - 1262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Linke, V. Adams, P. C. Schulze, S. Erbs, S. Gielen, E. Fiehn, S. Mobius-Winkler, A. Schubert, G. Schuler, and R. Hambrecht Antioxidative Effects of Exercise Training in Patients With Chronic Heart Failure: Increase in Radical Scavenger Enzyme Activity in Skeletal Muscle Circulation, April 12, 2005; 111(14): 1763 - 1770. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. MacNee Pulmonary and Systemic Oxidant/Antioxidant Imbalance in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 50 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Pilon, P. Dallaire, and A. Marette Inhibition of Inducible Nitric-oxide Synthase by Activators of AMP-activated Protein Kinase: A NEW MECHANISM OF ACTION OF INSULIN-SENSITIZING DRUGS J. Biol. Chem., May 14, 2004; 279(20): 20767 - 20774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sasaki, J. W. Elrod, P. Jordan, M. Itoh, T. Joh, A. Minagar, and J. S. Alexander CYP450 dietary inhibitors attenuate TNF-{alpha}-stimulated endothelial molecule expression and leukocyte adhesion Am J Physiol Cell Physiol, April 1, 2004; 286(4): C931 - C939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gielen, V. Adams, S. Mobius-Winkler, A. Linke, S. Erbs, J. Yu, W. Kempf, A. Schubert, G. Schuler, and R. Hambrecht Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure J. Am. Coll. Cardiol., September 3, 2003; 42(5): 861 - 868. [Abstract] [Full Text] [PDF]
|
|