Interferon‐γ activates multiple pathways to regulate the expression of the genes for major histocompatibility class II I‐Aβ, tumor necrosis factor and complement component C3 in mouse macrophages

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Abstract
The purpose of this study was to obtain additional information on the mechanism by which interferon-γ (IFN-γ) is able to regulate gene expression in macrophages. The expression of the genes for class II histocompatibility I-Aβ, tumor necrosis factor (TNF) and complement component C3 was assayed after treating bone marrow macrophages with IFN-γ. 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-γ treatment and reached a plateau after 4 h. In contrast, there was a lag of about 4 h before the level of I-Aβ RNA began to rise and a plateau was not reached until 48 h after the IFN-γ treatment began. C3 gene expression followed an intermediate time course between that for TNF and I-Aβ. Second, the expression of I-Aβ was inhibited when cells were treated with both IFN-γ 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-γ, after which cycloheximide had no effect on the expression of I-Aβ. Third, lipopolysaccharide abolished the IFN-γ-induced expression of I-Aβ, but enhanced the expression of TNF. Based on these observations, we conclude that IFN-γ must activate multiple pathways to regulate gene expression in macrophages.