Molecular Cloning of a Gene Selectively Induced by Gamma Interferon from Human Macrophage Cell Line U937

Abstract

A cDNA clone encoding a gamma interferon (IFN-γ)-inducible mRNA in human cells of the macrophage lineage was isolated and characterized. The corresponding gene, γ.1, was selectively induced by IFN-γ, responding a hundredfold better to IFN-γ than to IFN-α. The induction was rapid and transient, with maximal mRNA accumulation at about 3 h and decline to the basal level after 48 h. Transcriptional activation could be detected as early as 5 min after IFN-γ stimulation and accounted entirely for the mRNA accumulation. The induction of γ.1 by IFN-γ was cell-type restricted, being seen only in macrophages and endothelial cells. In addition, phorbol ester-induced differentiation of promyelocytic HL-60 cells and promonocytic THP-1 cells rendered the γ.1 gene inducible by IFN-γ. The 1.0-kilobase γ.1 cDNA sequence encoded a small predicted polypeptide of 38 amino acids and had a conserved sequence associated with rapidly turning over mRNAs. In vitro translation of the γ*1 transcript yielded a 4,000-dalton polypeptide.