Antisense inhibition of vitamin D receptor expression induces apoptosis in monoblastoid U937 cells.

摘要: The active vitamin D3 metabolite 1,25-dihydroxycholecalciferol (1,25(OH)2D3) acts as an antiproliferative and differentiating agent for the monoblastoid cell line U937 important immunologic mediator implicated particularly in function of cells belonging to monocyte/macrophage lineage. These effects are controlled by D receptor (VDR), a member steroid hormone family. objective this study was develop transfectants expressing antisense VDR mRNA, use these examine role 1,25(OH)2D3-VDR interaction A 2-kb cDNA insert (including complete coding region) cloned orientation into EBV episomal vector pMEP4 under control inducible promoter transfected U937. resultant line, DH42, hygromycin resistant, contained cDNA, expressed fewer VDRs than controls, showed substantial decrease response 1,25(OH)2D3. However, 1,25(OH)2D3 increased number macrophage surface Ags, including CD14 CD11b. subpopulation smaller did not express differentiation markers after cadmium stimulation. Cell cycle analysis shifts distribution from G1 S phase, which were more pronounced treatment. considerable proportion outside DNA fragmentation confirmed apoptosis. Thus, functional outcome transfection suggests that myelomonocytic lineage, expression may act protective mechanism against programmed death.