Mechanisms of inhibition of mouse myeloid leukemic cell differentiation by prostaglandin F2 alpha.
Mouse myeloid leukemia M1 cells were induced to differentiate in vitro into macrophages and granulocytes by various inducers, including dexamethasone. Prostaglandin F2 alpha inhibited the inductions by dexamethasone of phagocytic and lysozyme activities in M1 cells. Prostaglandin F2 alpha stimulated the production of differentiation-inhibiting activity (I-activity) in M1 cells. I-activity production by prostaglandin F2 alpha was decreased by simultaneous treatment with actinomycin D (5 ng/ml) but not with 5-fluoro-2'-deoxyuridine (10 ng/ml). The I-activity was inactivated by heating (70 degrees, 20 min) or by treatment with trypsin but not with mixed glycosidases or ribonuclease, suggesting that I-activity was due to a proteinous substance(s). B-Type prostaglandins also stimulated I-activity production, whereas A-, E- and D-type ones did not. Induction of prostaglandin E2. Retinoic acid stimulated the synthesis and release of prostaglandin F2 alpha and production of I-activity in M1 cells. Indomethacin completely inhibited induction of I-activity by retinoic acid. On the basis of these results, the relationship between I-activity production and prostaglandin F2 alpha production is discussed.
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015237:Dinoprost; D015232:Dinoprostone; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000473:pathology; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009113:Muramidase / Q000096:biosynthesis; D010587:Phagocytosis / Q000187:drug effects; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology
D011458:Prostaglandins E; D011460:Prostaglandins F; D014212:Tretinoin; D003907:Dexamethasone; D015237:Dinoprost; D009113:Muramidase; D015232:Dinoprostone