Interferon-γ inhibits the synthesis and release of renin from human decidual cells

Abstract

Experiments were performed to examine the effect of interferon-γ (IFNγ) 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 IFNγ 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 IFNγ was 5 ng/ml (290 pM). The inhibition of renin release in response to IFNγ was accompanied by a comparable inhibition of renin mRNA levels. In addition to inhibiting basal renin expression, IFNγ potentiated the inhibitory effect of tumor necrosis factor α (TNFα) on renin expression. IFNγ also inhibited basal renin release and potentiated the inhibitory effect of TNFα 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 IFNγ mRNA, and that both HLA-DR(+) and HLA-DR(-) cells express IFNγ receptors. Since IFNγ is expressed only by decidual macrophages, the results of this study strongly suggest that IFNγ inhibits the expression of decidual renin by a paracrine action.