Genomic organization and regulation of the human interleukin-18 gene

The human interleukin(IL)-18 is a key regulator of interferon(IFN)-gamma pr oduction and T-cell differentiation. Here we report the complete genomic st ructure and characterization of the 5'untranslated promoter region of the h uman IL-18 gene. The gene is composed of six exons and five introns, spanni ng approximately 19.5kb. Promoter activity of the 5'-flanking region was in vestigated with a luciferase reporter gene assay. Transient transfection st udies demonstrate a constitutive expression of the IL-18 gene in monocytic U937 and THP-1 cells. For this constitutive expression at least 92 base pai rs of the promoter region are essential as shown by consecutive 5' promoter deletions in both cell types. DNA protein binding experiments revealed spe cific binding of activated signal transducer and activator of transcription factor-5 (STAT5) but not of STAT3 to three consensus sequences upstream in the promoter region. Cotransfection of STAT5 resulted in increased inducti on of the IL-18 promoter in the U937 and THP-1 cells.