Inhibition by dexamethasone of human neutrophil apoptosis in vitro.
We investigated in this study the effect of a synthetic glucocorticoid hormone, dexamethasone (Dex), on apoptosis of human peripheral blood neutrophils. Dex inhibited spontaneous and tumor necrosis factor-alpha (TNF-alpha)-induced neutrophil apoptosis in a concentration- and time-dependent manner. This effect of Dex on neutrophil apoptosis was completely reversed by a glucocorticoid receptor antagonist, RU38486, and by cycloheximide. The decrease in sensitivity to TNF-alpha-induced apoptosis cannot be ascribed to a down-modulation of TNF receptors on these cells. These observations suggest that a glucocorticoid hormone participates in the regulation of neutrophil apoptosis and that inhibition of human neutrophil apoptosis by Dex is mediated through glucocorticoid-receptor-induced de novo synthesis of macromolecules. Possible mechanisms and implications of this phenomenon are discussed.
Kato
T
T
Department of Immunology and Parasitology, Yamagata, University School of Medicine, Japan.
Takeda
Y
Y
Nakada
T
T
Sendo
F
F
D017209:Apoptosis / Q000187:drug effects*; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000737:chemistry / Q000166:cytology*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D011965:Receptors, Glucocorticoid; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D003513:Cycloheximide