Interferon-y Inhibits the Synthesis and Release of Renin from Human Decidual Cells1

Abstract

Experiments were performed to examine the effect of interferon-gamma (IFN gamma) on the expression of renin by human uterine decidual cells and decidual macrophages. Exposure of a mixed population of decidual cells consisting of 80% decidualized stromal cells and 20% macrophages to IFN gamma for 4 days caused a dose-dependent inhibition of renin release beginning 2 days after exposure. Renin release on Day 4 was inhibited by a maximum of 83.9%, and the half-maximal effective dose of IFN gamma was 5 ng/ml (290 pM). The inhibition of renin release in response to IFN gamma was accompanied by a comparable inhibition of renin mRNA levels. In addition to inhibiting basal renin expression, IFN gamma potentiated the inhibitory effect of tumor necrosis factor alpha (TNF alpha) on renin expression. IFN gamma also inhibited basal renin release and potentiated the inhibitory effect of TNF alpha by highly purified populations of decidual stromal cells and decidual macrophages prepared by immunomagnetic separation with beads coupled to an anti-human leukocyte antigen (HLA-DR) antibody that binds macrophages but not stromal cells. Reverse transcription-polymerase chain reaction analysis showed that HLA-DR(+) cells express IFN gamma mRNA, and that both HLA-DR(+) and HLA-DR(-) cells express IFN gamma receptors. Since IFN gamma is expressed only by decidual macrophages, the results of this study strongly suggest that IFN gamma inhibits the expression of decidual renin by a paracrine action.