Mechanism of interferon-γ down-regulation of the interleukin 4-induced cd23/fcεrii expression in human B-cells : post-transcriptional modulation by interferon-γ

Abstract

It has been reported that the interleukin 4 (IL-4) specific induction of cell surface CD23 (Fc(ε)RII) is due down-regulated by interferon-γ (IFN-γ) in monocytes and B cells. However, the molecular level at which the inhibition occurs seems to vary depending on the cell types. In normal human B cells, IFN-γ inhibits the IL-4 induced de novo synthesis of CD23 at the level of gene expression. Analysis of inhibition kinetics suggested a rapid signal transmission by IFN-γ. Yet the inhibitory action of IFN-γ on CD23 mRNA accumulation appeared as a secondary response requiring a new protein synthesis. Through nuclear run-on transcription and mRNA stability studies, we further demonstrate that the IL-4 induced CD23 gene expression is down-regulated by IFN-γ mainly at post-transcriptional levels by decreasing mRNA stability.