title: Expression and induction by dexamethasone of ABC transporters and nuclear receptors in a human T-lymphocyte cell line.
abstract: The efficacy of drugs acting within lymphocytes, like antiretroviral drugs in the treatment of HIV infection, depends on their intracellular concentrations modulated by efflux proteins like ABCB1 (P-glycoprotein). In lymphocytes, two glucocorticoids, prednisone and prednisolone, have been shown to induce ABCB1 activity. Yet, no data exist regarding dexamethasone (DEX). We report the modulation of ABC transporters and nuclear receptors' expression by DEX in a commonly used model of human lymphocytes. CCRF-CEM cells were exposed to DEX (100 nM, 2 μM) for 24 to 72 hours. ABCB1 activity was measured using DiOC(6) efflux in flow cytometry. Gene expression levels were quantified by qRT-PCR. ABCB1 activity and mRNA expression increased with DEX concentrations and incubation times. DEX (1 μM, 24 h) increased significantly ABCB1 and GR mRNA expression levels by around 8- and 3.5-fold, respectively (P<10(-6)). ABCB1 induction by DEX in CCRF-CEM cells suggests a potential risk of interaction in lymphocytes when associating DEX to ABCB1 substrates in antiretroviral multitherapies in vivo.
authors.affiliation: EA 3620, Université Paris Descartes, Paris, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Manceau
authors.forename: Carole
authors.initials: C
authors.lastname: Giraud
authors.forename: Xavier
authors.initials: X
authors.lastname: Declèves
authors.forename: Frédéric
authors.initials: F
authors.lastname: Batteux
authors.forename: Christiane
authors.initials: C
authors.lastname: Chéreau
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chouzenoux
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Scherrmann
authors.forename: Bernard
authors.initials: B
authors.lastname: Weill
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Perrot
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tréluyer
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D018528:ATP-Binding Cassette Transporters; D005938:Glucocorticoids; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D003907:Dexamethasone