%0 Journal Article
%T Endotoxin-induced IL-6 promoter activation in skeletal muscle requires an NF-κB site
%A David Yeagley
%A Charles H Lang
%J International Journal of Interferon, Cytokine and Mediator Research
%D 2010
%I Dove Medical Press
%X David Yeagley, Charles H LangDepartment of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, USAAbstract: Previous studies in monocytes and other cell types have provided evidence of a role for the NF-百B pathway in interleukin 6 (IL-6) induction. The purpose of the present study was to examine the involvement of NF-百B in the induction of the IL-6 promoter in skeletal muscle cells by endotoxin (lipopolysaccharide [LPS]), tumor necrosis factor alpha (TNF汐) or IL-1汐. 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-百B 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-百B 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-百B-based promoter. This lack of effect was not due to a lack of NF-百B 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-百B site that does not bind to a consensus NF-百B 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, TNF汐, IL-1, myocytes, promoter activity, inflammation
%U http://www.dovepress.com/endotoxin-induced-il-6-promoter-activation-in-skeletal-muscle-requires-a3922