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Genome-wide analysis of vitamin D receptor (VDR) binding sites in THP-1 human monocyte-like cells highlighted the interleukin 8 gene, also known as chemokine CXC motif ligand 8 ( CXCL8 ). CXCL8 is a chemotactic cytokine with important functions during acute inflammation as well as in the context of various cancers. The nine genes of the CXCL cluster and the strong VDR binding site close to the  CXCL8  gene are insulated from neighboring genes by CCCTC-binding factor (CTCF) binding sites. Only  CXCL8 ,  CXCL6  and  CXCL1  are expressed in THP-1 cells, but all three are up-regulated primary 1,25-dihydroxyvitamin D 3  (1,25(OH) 2 D 3 ) target genes. Formaldehyde-assisted isolation of regulatory elements sequencing analysis of the whole CXCL cluster demonstrated 1,25(OH) 2 D 3 -dependent chromatin opening exclusively for the VDR binding site. In differentiated THP-1 cells the  CXCL8  gene showed a 33-fold higher basal expression, but is together with  CXCL6  and  CXCL1  still a primary 1,25(OH) 2 D 3  target under the control of the same genomic VDR binding site. In summary, both in undifferentiated and differentiated THP-1 cells the genes  CXCL8 ,  CXCL6  and  CXCL1  are under the primary control of 1,25(OH) 2 D 3  and its receptor VDR. Our observation provides further evidence for the immune-related functions of vitamin D.

Primary 1,25-Dihydroxyvitamin D3 Response of the Interleukin 8 Gene Cluster in Human Monocyte- and Macrophage-Like Cells