Selective DNA-binding activity of interleukin-10-stimulated STAT molecules in human monocytes

J Interferon Cytokine Res. 1999 Jun;19(6):679-85. doi: 10.1089/107999099313839.


It has been demonstrated that interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) have various reverse effects on macrophages; however, the molecular mechanism of this difference has not been fully understood. In this study, we analyzed the binding activity of IL-10- and IFN-gamma-activated STAT molecules to two kinds of GAS-motif sequences. IL-10-activated STAT1 could bind to the GAS-motif sequence in the promoter region of the Fcgamma receptor, but not to that in the promoter region of the COX-2 gene, whereas IFN-gamma-activated STAT1 and STAT5 could bind to both sequences. IL-10 inhibited IFN-gamma-induced STAT activation without newly synthesized protein. We further demonstrated that aspirin, but not dexamethasone, suppressed IFN-gamma-induced STAT activation. Taken together, these results suggest that IL-10-activated STAT1 has a specificity in binding to the GAS-motif sequences, whereas IFN-gamma-activated STAT1 and STAT5 have a broader spectrum in binding to the GAS-motif sequences. This may explain the difference between IL-10 and IFN-gamma in biological activity, and the inhibitory effect of IL-10 on IFN-gamma activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspirin / pharmacology
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • DNA-Binding Proteins / metabolism*
  • Dexamethasone / pharmacology
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-10 / pharmacology*
  • Isoenzymes / biosynthesis
  • Isoenzymes / drug effects
  • Membrane Proteins
  • Milk Proteins*
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / drug effects
  • STAT1 Transcription Factor
  • STAT5 Transcription Factor
  • Signal Transduction / physiology*
  • Stimulation, Chemical
  • Trans-Activators / metabolism*


  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • DNA-Binding Proteins
  • Isoenzymes
  • Membrane Proteins
  • Milk Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT5 Transcription Factor
  • Trans-Activators
  • Interleukin-10
  • Dexamethasone
  • Interferon-gamma
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Aspirin