1α-dihydroxyvitamin d3 and retinoic acid increase nuclear vitamin d receptor expression in monocytic THP-1 cells

Abstract

Background: 1α,25-Dihydroxyvitamin D3 [1,25(OH)2D3] and retinoic acid, such as all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9cRA), are known to induce differentiation of myeloid leukemia cells. Combined treatment effectively enhances the differentiation effect, particularly in monocytic leukemia cells. The underlying mechanism of this combined effect remains unknown. Materials and Methods: THP-1 monocytic leukemia cells were treated with 1,25(OH)2D3 in combination with 9cRA, ATRA or selective synthetic ligand for retinoic acid receptor (RAR) or retinoid X receptor (RXR), and the nuclear expression and function of vitamin D receptor (VDR) were examined. Results: Combined treatment with 1,25(OH)2D3 and RAR ligand, not RXR ligand, effectively increased nuclear VDR expression and induced expression of the VDR target gene cathelicidin antimicrobial peptide (CAMP) in a geneselective manner. Conclusion: Combination of 1,25(OH)2D3 plus RAR ligand is effective in induction of nuclear VDR expression and of target gene.