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.
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.
Celada
A
A
Cancer Research Center, La Jolla, CA 92037.
Klemsz
M J
MJ
Maki
R A
RA
D000818:Animals; D001854:Bone Marrow Cells; D003176:Complement C3 / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D003176:Complement C3; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003513:Cycloheximide