title: Cortisone counteracts apoptosis-inducing effect of cortisol in human peripheral-blood mononuclear cells.
abstract: Glucocorticoids (GCs) have been considered to regulate immune cell systems through induction of apoptosis in thymocytes and mature peripheral-blood lymphocytes. Here we report that apoptosis induced by cortisol in mitogen-activated peripheral-blood mononuclear cells (PBMC) is suppressed by cortisone, an oxidized metabolite of cortisol. Apoptosis in PBMCs is quantified by a cell death ELISA procedure, which can specifically detect fragmented DNA. Cortisol induced PBMC-apoptosis at concentrations more than 10 ng/ml (28 nM) in concanavalin A-stimulated PBMCs and cortisone suppressed this apoptosis at a concentration range of 1-10,000 ng/ml (2.8-28,000 nM) dose-dependently. Prednisone, a synthetic oxidized-GC, also suppressed the apoptosis-inducing effect of cortisol in a dose-dependent manner. Suppression of cortisol-induced apoptosis by cortisone was consistently observed in PBMCs derived from 16 healthy subjects. Examination for inhibitory activities of the steroids against [3H]dexamethasone binding to PBMCs suggested that cortisone can bind cellular GC-receptors (GC-Rs), but the affinity of cortisone to GCRs is 1/30 or less than that of cortisol. The results raised a possible role of cortisone in cortisol-mediated regulation of apoptosis in activated human PBMCs. The counteracting action of cortisone against cortisol-induced apoptosis may take place partially through intervention of GC-receptors (GC-Rs), but may also be due to unknown pathway(s) different from those mediated by cellular GC-Rs.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan. hiranot@ps.toyaku.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Hirano
authors.forename: A
authors.initials: A
authors.lastname: Horigome
authors.forename: M
authors.initials: M
authors.lastname: Takatani
authors.forename: K
authors.initials: K
authors.lastname: Oka
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D003348:Cortisone / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000037:antagonists & inhibitors*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D009336:Necrosis; D011241:Prednisone / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000097:blood / Q000187:drug effects* / Q000502:physiology
chemical_list: D011965:Receptors, Glucocorticoid; D003208:Concanavalin A; D003907:Dexamethasone; D003348:Cortisone; D011241:Prednisone; D006854:Hydrocortisone