Glucocorticoid, interleukin-2, and prostaglandin interactions in a clonal human leukemic T-cell line.
We have studied the growth effects of conditioned media, interleukin-2 and PGE prostaglandin analogs on the glucocorticoid-sensitive human leukemic T-cell clone, CEM-C7. After 4 days, the glucocorticoid dexamethasone at approximately 10 nM kills 50% of CEM-C7 cells. To test the hypothesis that glucocorticoid-mediated lymphocytolysis was due to suppression of lymphokine expression only, we attempted to protect CEM-C7 cells from lysis by provision of lymphokine(s). Conditioned media from interleukin-2 secreting Jurkat T-cells as well as the glucocorticoid-insensitive, but receptor positive clone, CEM-C1, failed to prevent lymphocytolysis; exogenous interleukin-2 also did not provide protection. There were complex, biphasic interactions between dexamethasone and the synthetic PGEs, enisoprost and enisoprost free acid. Low doses of enisoprost alone (0.01 to 1 microgram/ml) stimulated growth, and in combinations completely reversed the growth inhibitory effects of 10 nM dexamethasone. Higher concentrations of enisoprost were inherently lethal and were additive to the steroid effect. Thus the glucocorticoid-induced lymphocytolysis in this human leukemic T-cell line may be modified biphasically by PGE prostaglandins, depending on their concentration. However, interleukin-2 or components in the conditioned media assayed had no effect in ameliorating the lethal response to glucocorticoid.
Johnson
B H
BH
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
Dean
R R
RR
Moran
S M
SM
Thompson
E B
EB
D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015458:Leukemia, T-Cell / Q000473:pathology*; D011458:Prostaglandins E / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D003470:Culture Media; D005938:Glucocorticoids; D007376:Interleukin-2; D011458:Prostaglandins E; D003907:Dexamethasone; D000527:Alprostadil; C054594:enisoprost