Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8.
To identify possible regulatory sites of the gene expression, we cloned the genomic DNA of human monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8), whose mRNA is induced by IL-1 or TNF and determined its entire nucleotide sequence. The results show that the MDNCF/IL-8 gene consists of 4 exons and 3 introns with a single "CAT"- and "TATA"-like structure. The 5'-flanking region of MDNCF/IL-8 gene shows no overall sequence similarity with that of other cytokine and acute phase reactant genes whose production is also affected by IL-1 and TNF. The 5' flanking region, however, contains potential binding sites for several nuclear factors including activation factor-1, activation factor-2, IFN regulatory factor-1, and hepatocyte nuclear factor-1. In addition, the glucocorticoid responsive element and heat shock element were located in the 5'-flanking region. Inasmuch as PMA induces MDNCF/IL-8 mRNA accumulation in human PBMC and a glucocorticoid inhibits the induction of MDNCF/IL-8 mRNA by LPS, the expression of this gene is probably regulated by interaction of these nuclear factors with the 5'-flanking DNA.
Mukaida
N
N
Division of Cancer Treatment, National Cancer Institute, Frederick Cancer Research Facility, MD 21701-1013.
Shiroo
M
M
Matsushima
K
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D002630:Chemotactic Factors / Q000235:genetics* / Q000302:isolation & purification; D003001:Cloning, Molecular; D015342:DNA Probes; D005796:Genes; D006801:Humans; D016209:Interleukin-8; D007378:Interleukins / Q000235:genetics* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D009000:Monocytes / Q000032:analysis*; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D010455:Peptides / Q000235:genetics* / Q000302:isolation & purification; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid
D002630:Chemotactic Factors; D015342:DNA Probes; D016209:Interleukin-8; D007378:Interleukins; D010455:Peptides