Dexamethasone modifies the functional responses of the granulocytic differentiating HL-60 cells.
We have studied the effect of dexamethasone on the granulocytic differentiation of the human promyelocytic cell line HL-60 induced by treatment with retinoic acid (RA) or dimethyl sulphoxide (DMSO). Dexamethasone potentiated the immunophenotypic and functional parameters associated with the granulocytic differentiation induced by RA, including changes in CD11b and CD71 expression, inhibition of cell proliferation, enhancement of secretory and oxidative responses and increase of the phospholipase C (PLC), phospholipase A2 (PLA2) and phospholipase D (PLD) activities. However, dexamethasone had selective effects on several parameters of DMSO-induced cell differentiation. Dexamethasone inhibited the DMSO-induced increase of CD11b cell surface expression as well as the oxidative response and PLD activation triggered by 4 beta-phorbol 12-myristate 13-acetate. Nevertheless, dexamethasone potentiated the receptor-mediated PLC activation and the receptor-mediated secretory and oxidative responses in DMSO-treated cells. Unlike RA-treated HL-60 cells, the DMSO-treated cells contained high values of activatable PLA2 activity which were not affected by dexamethasone. Thus dexamethasone affected differently functional parameters and effector systems of granulocytic HL-60 cells, depending on the differentiation agent used. Dexamethasone by itself did not induce HL-60 cell differentiation, but enhanced the receptor- and non-receptor-mediated secretory responses and induced the appearance of stimulated PLA2 activity in undifferentiated HL-60 cells. These data provide evidence for the selective modulation of functional responses by dexamethasone through alterations in signalling processes.
Collado-Escobar
D
D
Centro de Investigaciones Biológicas, C.S.I.C., Madrid, Spain.
Mollinedo
F
F
D015703:Antigens, CD / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D018845:CD11 Antigens; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006098:Granulocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D010739:Phospholipase D / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011990:Receptors, Transferrin; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D018845:CD11 Antigens; C068126:CD71 antigen; D011990:Receptors, Transferrin; D014212:Tretinoin; D003907:Dexamethasone; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide