Promoter analysis of the human interleukin-8 receptor genes, IL-8RA and IL-8RB

Two distinct receptors for the neutrophil chemoattractant IL-8 have been cloned, designated IL-8RA and -B. Both receptors are abundantly expressed on unstimulated mature neutrophils. To understand the tissue-specific expression and to identify gene-regulatory elements we have cloned, sequenced and characterized both human IL-8R genes, IL-8RA and -B. The open reading frames and 3'-untranslated regions were entirely encoded by a single exon. The promoters of both IL-8R-genes appeared to be very similar: A non-classical TATA-box and a GC-rich 5'-flanking region was identified immediately upstream of the transcription start site. These minimal promoters were sufficient to generate constitutive activity in CAT-expression assays. A G-CSF responsive element was mapped within the first 118 nucleotides upstream of the transcription start site of the IL-8RB gene. Expression analyses of additional upstream regions suggested that both IL-8R-promoters are negatively controlled by silencer elements, which could be counteracted by stimulation with G-CSF.