IFN-γ does not mimic the catabolic effects of TNF-α

Melissa A. Smith, Jennifer S. Moylan, Jeffrey D. Smith, Wei Li, Michael B. Reid

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Cachexia is common in chronic inflammatory diseases and is attributed, in part, to an elevation of circulating proinflammatory cytokines. TNF-α is the prototype in this category. IFN-γ is also thought to play a role, but the evidence supporting this model is primarily indirect. To determine the direct effects of IFN-γ stimulation on muscle cells, we selected key components of the procatabolic signaling pathways by which TNF-α stimulates protein loss. We tested two hypotheses: 1) IFN-γ mimics TNF-α signaling by increasing intracellular oxidant activity and activating MAPKs and NF-κB and 2) IFN-γ increases the expression of the ubiquitin ligases atrogin1/MAFbx and muscle-specific ring finger protein 1 (MuRF1). Results showed that treatment with IFN-γ at 60 ng/ml increased Stat1 phosphorylation after 15 min, indicating receptor activation. IFN-γ had no effect on cytosolic oxidant activity, as measured by 2′,7′- dichlorofluorescein oxidation. Nor did IFN-γ activate JNK, ERK1/2, or p38 MAPK, as assessed by Western blot. Treatment for up to 60 min did not decrease IκB-α protein levels, as measured by Western blot analysis, or the DNA binding activity of NF-κB, as measured by EMSA. After 6 h, IFN-γ decreased Akt phosphorylation and increased atrogin1/MAFbx and MuRF1 mRNA. Daily treatment for up to 72 h did not alter adult fast-type myosin heavy chain content or the total protein-to-DNA ratio. These data show that responses of myotubes to IFN-γ and TNF-α differ markedly and provide little evidence for a direct catabolic effect of IFN-γ on muscle.

Original languageEnglish
Pages (from-to)C1947-C1952
JournalAmerican Journal of Physiology - Cell Physiology
Issue number6
StatePublished - Dec 2007


  • Atrophy
  • C2C12
  • Cachexia
  • Interferon-γ
  • Oxidative stress
  • Skeletal muscle
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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