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Mediators of Inflammation
Volume 2013, Article ID 171437, 18 pages
http://dx.doi.org/10.1155/2013/171437
Research Article

TNF-α and IFN-s-Dependent Muscle Decay Is Linked to NF- B- and STAT-1α-Stimulated Atrogin1 and MuRF1 Genes in C2C12 Myotubes

1Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences—SGGW, Nowoursynowska 159, 02-776 Warsaw, Poland
2Electron Microscopy Platform, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland

Received 4 July 2013; Revised 9 September 2013; Accepted 4 October 2013

Academic Editor: Elaine Hatanaka

Copyright © 2013 Barbara Pijet et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

TNF-α was shown to stimulate mitogenicity in C2C12 myoblasts. Selected cytokines TNF-α, IFNα, or IFNγ reduced the expression of myosin heavy chain (MyHC IIa) when given together. Molecular mechanisms of cytokine activities were controlled by NF-κB and JAK/STAT signaling pathways, as metabolic inhibitors, curcumin and AG490, inhibited some of TNF-α and IFNα/IFNγ effects. Insulin was hardly antagonistic to TNF-α- and IFNα/IFNγ-dependent decrease in MyHC IIa protein expression. Cytokines used individually or together also repressed myogenesis of C2C12 cells. Moreover, TNF-α- and IFNα/IFNγ-dependent effects on C2C12 myotubes were associated with increased activity of Atrogin1 and MuRF1 genes, which code ubiquitin ligases. MyHC IIa gene activity was unaltered by cytokines. Inhibition of NF-κB or JAK/STAT with specific metabolic inhibitors decreased activity of Atrogin1 and MuRF1 but not MyHC IIa gene. Overall, these results suggest cooperation between cytokines in the reduction of MyHC IIa protein expression level via NF-κB/JAK/STAT signaling pathways and activation of Atrogin1 and MuRF1 genes as their molecular targets. Insulin cotreatment or pretreatment does not protect against muscle decay induced by examined proinflammatory cytokines.