Interferon-gamma activates multiple pathways to regulate the expression of the genes for major histocompatibility class II I-A beta, tumor necrosis factor and complement component C3 in mouse macrophages

Eur J Immunol. 1989 Jun;19(6):1103-9. doi: 10.1002/eji.1830190621.


The purpose of this study was to obtain additional information on the mechanism by which interferon-gamma (IFN-gamma) is able to regulate gene expression in macrophages. The expression of the genes for class II histocompatibility I-A beta, tumor necrosis factor (TNF) and complement component C3 was assayed after treating bone marrow macrophages with IFN-gamma. Each gene displayed a characteristic pattern of regulation. First, the increase in the level of RNA for each gene followed different kinetics. The level of TNF RNA increased within 15 min after IFN-gamma treatment and reached a plateau after 4 h. In contrast, there was a lag of about 4 h before the level of I-A beta RNA began to rise and a plateau was not reached until 48 h after the IFN-gamma treatment began. C3 gene expression followed an intermediate time course between that for TNF and I-A beta. Second, the expression of I-A beta was inhibited when cells were treated with both IFN-gamma and cycloheximide, while the expression of TNF and C3 was not. Interestingly, the sensitivity to cycloheximide only lasted 30 min following the addition of IFN-gamma, after which cycloheximide had no effect on the expression of I-A beta. Third, lipopolysaccharide abolished the IFN-gamma-induced expression of I-A beta, but enhanced the expression of TNF. Based on these observations, we conclude that IFN-gamma must activate multiple pathways to regulate gene expression in macrophages.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Cells
  • Complement C3 / genetics*
  • Cycloheximide / pharmacology
  • Gene Expression Regulation / drug effects
  • Histocompatibility Antigens Class II / genetics*
  • Interferon-gamma / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Macrophages / physiology*
  • Mice
  • Mice, Inbred DBA
  • Recombinant Proteins
  • Time Factors
  • Transcription, Genetic / drug effects
  • Tumor Necrosis Factor-alpha / genetics*


  • Complement C3
  • Histocompatibility Antigens Class II
  • Lipopolysaccharides
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Cycloheximide