title: Aryl hydrocarbon receptor regulates CYP1B1 but not ABCB1 and ABCG2 in hCMEC/D3 human cerebral microvascular endothelial cells after TCDD exposure.
abstract: The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor activated by a variety of widespread persistent environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It can transactivate the expression of several target genes. Recently AhR transcripts were detected in isolated human brain microvessels and in the hCMEC/D3 human cerebral microvascular endothelial cell line, an in vitro model of the human cerebral endothelium. To date AhR implication in the co-regulation of ABCB1, ABCG2 and CYP1B1 at human cerebral endothelium has not been addressed. Here we investigated whether AhR could co-regulate ABCB1, ABCG2 and CYP1B1 expressions in the hCMEC/D3 cell line. Exposure to TCDD induced a concentration-dependent increase in CYP1B1 expression. We demonstrated AhR involvement in the TCDD-mediated increase in CYP1B1 expression by using small interfering RNA against AhR. Western blotting analysis also revealed an increase in CYP1B1 protein expression following TCDD exposure in hCMEC/D3. Regarding ABCB1 and ABCG2, exposure to TCDD had no effect on their protein expressions and functional activities. In conclusion our data indicated a differential modulation of CYP1B1 and ABCB1/ABCG2 expressions in hCMEC/D3 cells following TCDD exposure.
authors: INSERM, UMR-S 1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France.
authors: Aude
authors: A
authors: Jacob
authors: INSERM, UMR-S 1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France.
authors: Sophie
authors: S
authors: Potin
authors: INSERM, UMR-S 1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France.
authors: Hélène
authors: H
authors: Chapy
authors: INSERM, UMR-S 1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France.
authors: Dominique
authors: D
authors: Crete
authors: INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Paris, France.
authors: Fabienne
authors: F
authors: Glacial
authors: INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Paris, France.
authors: Kayathiri
authors: K
authors: Ganeshamoorthy
authors: INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Paris, France.
authors: Pierre-Olivier
authors: PO
authors: Couraud
authors: INSERM, UMR-S 1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France.
authors: Jean-Michel
authors: JM
authors: Scherrmann
authors: INSERM, UMR-S 1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France. Electronic address: xavier.decleves@parisdescartes.fr.
authors: Xavier
authors: X
authors: Declèves
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002460:Cell Line; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D055806:Microvessels / Q000187:drug effects; D009363:Neoplasm Proteins / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1
keywords: ATP-binding cassette transporters; Aryl hydrocarbon receptor; Blood–brain barrier; CYP1B1; hCMEC/D3