Prostaglandin E2 regulates vitamin D receptor expression, vitamin D-24-hydroxylase activity and cell proliferation in an adherent human myeloid leukemia cell line (Ad-HL60).
The effects of prostaglandin E2, forskolin, and phorbol 12-myristate 13-acetate on cell proliferation, cell surface antigen expression, vitamin D-24-hydroxylase activity and vitamin D receptor (VDR) expression have been studied in an adherent variant (Ad-HL60) of the human HL60 promyelomonocytic leukemia cell line. Ad-HL60 cells have a more differentiated phenotype than the nonadherent HL60 cells from which they were derived and, unlike the parent cell line, constitutively express vitamin D-24-hydroxylase activity. Treatment of Ad-HL60 cells with 1 microM PGE2 resulted in a decrease in the rate of cell proliferation (cell numbers were approximately 23% of control values after 72 h treatment), a change in expression of leukocyte surface antigens (decreased CD13 and CD14, increased CD11b and CD49d expression), an increase in the synthesis of 24,25-dihydroxyvitamin D3 from substrate 25-hydroxyvitamin D3 (control 5.76 +/- 0.17, 72 h PGE2-treated cells 12.10 +/- 1.90 pmol/h/10(6) cells), and an increase in receptors for the active metabolite of vitamin D, 1 alpha,25-dihydroxyvitamin D3, from 3910 to 11285 receptors per cell in control and 7-day treated cells, respectively. Prostaglandin E2 may be acting via a mechanism involving cyclic AMP in these cells, as we have also demonstrated that 10 microM forskolin, an adenylate cyclase activator, has similar effects. Phorbol 12-myristate 13-acetate had little effect on any of the parameters measured in this cell line.
University Department of Medicine, Manchester Royal Infirmary, UK.
S J
SJ
Smith
L M
LM
Green
M E
ME
Hayes
E B
EB
Mawer
D015650:24,25-Dihydroxyvitamin D 3 / Q000378:metabolism; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D010641:Phenotype; D018167:Receptors, Calcitriol / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D065668:Vitamin D3 24-Hydroxylase
D015703:Antigens, CD; D018167:Receptors, Calcitriol; D005576:Colforsin; D015650:24,25-Dihydroxyvitamin D 3; D003577:Cytochrome P-450 Enzyme System; D000242:Cyclic AMP; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate