Back to Archived Journals » International Journal of Interferon, Cytokine and Mediator Research » Volume 2

Endotoxin-induced IL-6 promoter activation in skeletal muscle requires an NF-κB site

Authors Yeagley D, Lang CH

Published 25 January 2010 Volume 2010:2 Pages 9—21

DOI https://doi.org/10.2147/IJICMR.S6690

Review by Single-blind

Peer reviewer comments 3


David Yeagley, Charles H Lang

Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, USA

Abstract: Previous studies in monocytes and other cell types have provided evidence of a role for the NF-κB pathway in interleukin 6 (IL-6) induction. The purpose of the present study was to examine the involvement of NF-κB in the induction of the IL-6 promoter in skeletal muscle cells by endotoxin (lipopolysaccharide [LPS]), tumor necrosis factor alpha (TNFα) or IL-1α. Transfection of C2C12 mouse myocytes with a luciferase reporter under the control of the IL-6 promoter indicated each immunomodulator enhanced IL-6 promoter activity. Mutation and inhibitor studies indicate this response was dependent on the IL-6 NF-κB binding site, but independent of NF-IL6, AP-1, CREB or C/EBP. Cotransfection with an expression vector which constitutively activates the RelA pathway increased IL-6 promoter activity, and activity could not be further enhanced by cytokines or LPS. However, cotransfecting various dominant negative upstream NF-κB kinase expression vectors which inhibited RelA or RelB pathways either individually or in combination had no effect on LPS-induced activation of the IL-6 promoter, but abolished induction from a NF-κB-based promoter. This lack of effect was not due to a lack of NF-κB pathway activation in C2C12 myocytes because both Western analysis and EMSA supershifting showed an LPS-induced increase in nuclear RelA and RelA phosphorylation. However, another protein was observed bound to the IL-6 NF-κB site that does not bind to a consensus NF-κB site. The present findings provide novel insights on inflammation-induced stimulation of IL-6 promoter activity in skeletal muscle which is an important but non-traditional component of the innate immune system.
Keywords: lipopolysaccharide, TNFα, IL-1, myocytes, promoter activity, inflammation

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]