Identification of a phorbol ester-responsive element in the interferon-gamma receptor 1 chain gene.

Human monocytic leukemia THP-1 cells differentiate into macrophage-like cells when treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). During this process, interferon-gamma (IFN-gamma)-inducible expression of human leukocyte antigen-DR alpha is markedly enhanced. The enhancement of human leukocyte antigen-DR alpha expression is at least due to the TPA-dependent induction of the IFN-gamma receptor 1 chain and IFN-gamma receptor 2 chain genes. Here we have studied the mechanism of TPA-induced up-regulation of the IFN-gamma receptor 1 chain gene. Reporter gene analyses of 5'-deletion constructs of the IFN-gamma receptor 1 gene (IFNGR1) promoter indicated that the critical region for control of transcription and the TPA-responsive element (TRE) were present in the -128 to -109 base pair (bp) region. We confirmed that this region of the IFNGR1 promoter was responsive to TPA-induced signals by using a reporter construct whose promoter consisted of the -128 to -109 bp fragment and the minimal herpes simplex virus thymidine kinase promoter. Moreover, a supershift assay indicated that Sp1 bound to this TRE in TPA-treated THP-1 cells. These results suggest that in TPA-treated cells the binding of Sp1 to the TRE of the IFNGR1 promoter causes the up-regulation of this gene.