PROMOTER ANALYSIS OF THE HUMAN INTERLEUKIN-8 RECEPTOR GENES, IL-8RA AND IL-8RB

Two distinct receptors for the neutrophil chemoattractant IL-8 have be en cloned, designated IL-8RA and -B. Both receptors are abundantly exp ressed on unstimulated mature neutrophils, To understand the tissue-sp ecific expression and to identify gene-regulatory elements we have clo ned, sequenced and characterized both human IL-8R genes, IL-8RA and -B . The open reading frames and 3'-untranslated regions were entirely en coded by a single exon. The promoters of both IL-8R-genes appeared to be very similar: A non-classical TATA-box and a CC-rich 5'-flanking re gion was identified immediately upstream of the transcription start si te. These minimal promoters were sufficient to generate constitutive a ctivity in CAT-expression assays. A G-CSF responsive element was mappe d within the first 118 nucleotides upstream of the transcription start site of the IL-8RB gene. Expression analyses of additional upstream r egions suggested that both IL-8R-promoters are negatively controlled b y silencer elements, which could be counteracted by stimulation with G -CSF.