Genomic organization, sequence and transcriptional regulation of the human CXCL 11 gene

• Published in: Biochimica et biophysica acta 1999-07, Vol.1446 (1), p.167-172
• Main Authors: Tensen, Cornelis P., Flier, Jacoba, Rampersad, Sharita S., Sampat-Sardjoepersad, Shakun, Scheper, Rik J., Boorsma, Dick M., Willemze, Rein
• Format: Article
• Language: English
• Subjects: Base Sequence; Cell Line; Chemokine CXCL11; Chemokines, CXC - chemistry; Chemokines, CXC - genetics; Exons; Genomic Library; Humans; Introns; Molecular Sequence Data; Polymerase Chain Reaction; Promoter Regions, Genetic; RNA, Messenger - metabolism; Transcription, Genetic - drug effects
• ISSN: 0167-4781; 0006-3002; 1879-2634
• DOI: 10.1016/S0167-4781(99)00084-6

CXCL 11, encoded by the cDNA sequences designated β-R1, H-174, or I-TAC, is a CXC chemokine ligand for CXCR3 and assumed to be involved in inflammatory diseases characterized by the presence of activated T-cells. We here describe the genomic organization (four exons interrupted by three introns of 585, 98 and 230 bp) and sequence including 960 bp from the immediate 5′-upstream region of the human CXCL 11 gene. Within the promoter region, consensus sequences for regulatory elements (ISRE, GAS, NF-κB) important for cytokine-induced gene transcription were identified. The effect of (pro)inflammatory cytokines on CXCL 11 mRNA expression in monocytic cell lines (THP-1, U937) and primary cultures of dermal fibroblasts and endothelial cells were examined using Northern blot analysis. For these cell types, IFN-γ was a potent inducer of CXCL 11 transcription, which was synergistically enhanced by TNF-α.