Genomic organization, sequence and transcriptional regulation of the humanCXCL 11(1) gene

CXCL 11, encoded by the cDNA sequences designated beta-R1, H-174, or I-TAC, is a CXC chemokine ligand for CXCR3 and assumed to be involved in inflamma tory diseases characterized by the presence of activated T-cells. We here d escribe the genomic organization (four exons interrupted by three introns o f 585, 98 and 230 bp) and sequence including 960 bp from the immediate 5'-u pstream region of the human CXCL 11 gene. Within the promoter region, conse nsus sequences for regulatory elements (ISRE, GAS, NF-kappa B) important fo r cytokine-induced gene transcription were identified. The effect of (pro)i nflammatory cytokines on CXCL 11 mRNA expression in monocytic cell lines (T HP-1, U937) and primary cultures of dermal fibroblasts and endothelial cell s were examined using Northern blot analysis. For these cell types, IFN-gam ma was a potent inducer of CXCL 11 transcription, which was synergistically enhanced by TNF-alpha. (C) 1999 Elsevier Science B.V. All rights reserved.