Structure, genomic organization, and expression of the human interleukin- 8 receptor B gene

Two distinct receptors for the chemoattractant interleukin-8 (designated IL-8RA and -B) have been cloned recently. The receptors are expressed almost exclusively on neutrophils and myelomonocytic cell lines. In an attempt to understand the tissue-specific expression and to identify transcriptional regulatory elements we have cloned, sequenced, and characterized the human IL-8RB gene. The gene consists of 3 exons, interrupted by two introns of 3 and 5.4 kilobases (kb). A 1065-base pair open reading frame is encoded entirely in the third exon. A 1.4-kb 3'-untranslated region contains clustered AU-rich elements, similar to those described for genes regulated by altering mRNA stability. The start site of transcription was mapped by a modified rapid amplification of cDNA ends technique and revealed an unexpectedly long 5'-untranslated region of 423 base pairs. A TATA box equivalent was found in the 5'-flanking region 20 nucleotides upstream of the start of the first exon. The promoter was separated from the ATG-initiation codon by 8.75 kb. Comparison of the IL-8RB promoter with the promoter region of the receptor for another chemoattractant ligand, the bacterial peptide f- Met-Leu-Phe, revealed 3 novel but conserved motifs occupying similar positions. The immediate 5'-flanking region was GC-rich with 3 SP-1-like and 2 AP-2 sites identified in close proximity to the transcription start site. This essential promoter region was found to be responsible for constitutive expression, inducible by granulocyte colony-stimulating factor and controlled by silencer elements located further upstream between positions -779 and - 118.