1,25-dihydroxyvitamin D-3 suppresses the expression of the VCAM-1 receptor, VLA-4 in human leukemic HL-60 cells

Very late antigen-4 (VLA-4) is the complex with alpha 4 and beta 1 integrin s, which is the receptors to fibronectin and VCAM-1. We evaluate the effect of 1,25(OH)(2)D-3 on the expression of VLA-4 in human leukemic HL-60, U937 cells and human melanoma A375 cells. Flow cytometric analysis demonstrate that the expression of alpha 4 integrin is negatively regulated in the cell lines we studied. The expression of beta 1 integrin is also decreased in H L-60 and U937 cells. The mRNA expression of alpha 4 integrin is significant ly decreased by the treatment with 1,25(OH)(2)D-3, whereas 1,25(OH)(2)D-3 d oes not alter the expression of beta 1 mRNA. The adhesion assay demonstrate that the number of adherent cells treated with 1,25(OH)(2)D-3 is significa ntly lower than that untreated on VCAM-1-coated wells. Because VCAM-1 is hi ghly expressed in the endothelial cells, it is possible that 1,25(OH)(2)D-3 prevents the attachment of the cells from the endothelial cells in vivo. ( C) 1999 Academic Press.