IL-1β stimulates IL-6 production in cultured skeletal muscle cells through activation of MAP kinase signaling pathway and NF-κB

Guangjo Luo, Dan D. Hershko, Bruce W. Robb, Curtis J. Wray, Per Olof Hasselgren

Research output: Contribution to journalArticle

82 Scopus citations


Recent studies suggest that the skeletal muscle may be a significant site of IL-6 production in various conditions, including exercise, inflammation, hypoperfusion, denervation, and local muscle injury. The mediators and molecular mechanisms regulating muscle IL-6 production are poorly understood. We tested the hypothesis that IL-6 production in muscle cells is regulated by IL-1β and that mitogen-activated protein (MAP) kinase signaling and NF-κB activation are involved in IL-1β-induced IL-6 production. Cultured C2C12 cells, a mouse skeletal muscle cell line, were treated with different concentrations (0.1-2 ng/ml) of IL-1β in the absence or presence of the p38 MAP kinase inhibitor SB-208350 or the p42/44 inhibitor PD-98059. Protein and gene expression of IL-6 were determined by ELISA and real-time PCR, respectively. NF-κB DNA binding activity was determined by electrophoretic mobility shift assay and by transfecting myocytes with a luciferase reporter plasmid containing a promoter construct with multiple repeats of NF-κB binding site. Treatment of myotubes with IL-1β resulted in a dose- and time-dependent increase of IL-6 production accompanied by an ∼25-fold increase in IL-6 mRNA levels. IL-1β stimulated NF-κB DNA binding activity and gene activation. SB-208350 and PD-98059 inhibited the increase in IL-6 production induced by IL-1β. The present results support the concept that skeletal muscle is an important site of IL-6 production. In addition, the results suggest the IL-1β regulates muscle IL-6 production at least in part by activating the MAP kinase pathway and NF-κB.

Original languageEnglish (US)
Pages (from-to)R1249-R1254
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number5 53-5
StatePublished - May 1 2003
Externally publishedYes


  • Cytokines
  • Interleukin-6 production
  • Mitogen-activated protein kinase
  • Nuclear factor-κB

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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