Endotoxin-induced il-6 promoter activation in skeletal muscle requires an nf-κb site

David Yeagley, Charles H. Lang

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9-21
Number of pages13
JournalInternational Journal of Interferon, Cytokine and Mediator Research
Volume2
Issue number1
StatePublished - Apr 30 2010

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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