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

Antonio Celada, Michael J. Klemsz, Richard A. Maki

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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.

Original languageEnglish (US)
Pages (from-to)1103-1109
Number of pages7
JournalEuropean Journal of Immunology
Volume19
Issue number6
DOIs
StatePublished - Jun 1989

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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