BACKGROUND: 1α,25-Dihydroxyvitamin D[1,25(OH)D] 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)Din 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)Dand RAR ligand, not RXR ligand, effectively increased nuclear VDR expression and induced expression of the VDR target gene cathelicidin antimicrobial peptide (CAMP) in a gene-selective manner.
CONCLUSION: Combination of 1,25(OH)Dplus RAR ligand is effective in induction of nuclear VDR expression and of target gene.