title: Aryl hydrocarbon receptor upregulates IL-1β expression in hCMEC/D3 human cerebral microvascular endothelial cells after TCDD exposure.
abstract: The AhR is a cytosolic ligand-dependent transcription factor activated by both endogenous and exogenous chemicals. It can regulate expression of many target genes including some inflammatory cytokines and chemokines. To date AhR implication in the regulation of inflammatory cytokines and chemokines at human cerebral endothelium has not been addressed. In the present study, we investigated whether AhR could regulate the expression of two pro-inflammatory cytokines and one chemokine i.e. IL-1β, IL-6 and IL-8 in the hCMEC/D3 human cerebral microvascular endothelial cell line. Exposure to TCDD increased IL-1β mRNA expression levels in hCMEC/D3. By using small interfering RNA against AhR we demonstrated that TCDD effects on IL-1β expression were mediated through AhR activation. Regarding IL-6 and IL-8, TCDD exposure had little or no effect on their mRNA levels in hCMEC/D3. In conclusion, our findings suggest that AhR-mediated IL-1β regulation in cerebral endothelium could induce BBB breakdown and contribute to the pathogenesis of a variety of neurologic disorders.
authors.affiliation: 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.forename: Aude
authors.initials: A
authors.lastname: Jacob
authors.affiliation: INSERM, UMR-S 1124, Toxicologie Pharmacologie et Signalisation cellulaire, 45 rue des Saints-Pères, 75006 Paris, France; Université Paris Descartes, ComUE Sorbonne Paris Cité, 45 rue des Saints-Pères, 75006 Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Tomkiewicz-Raulet
authors.affiliation: 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.forename: Charlotte
authors.initials: C
authors.lastname: Jamet
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
authors.forename: Reina
authors.initials: R
authors.lastname: Bendayan
authors.affiliation: Université Paris Descartes, UMR-CNRS 8638, Paris F-75006, France.
authors.forename: France
authors.initials: F
authors.lastname: Massicot
authors.affiliation: INSERM, UMR-S 1124, Toxicologie Pharmacologie et Signalisation cellulaire, 45 rue des Saints-Pères, 75006 Paris, France; Université Paris Descartes, ComUE Sorbonne Paris Cité, 45 rue des Saints-Pères, 75006 Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Coumoul
authors.affiliation: 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.forename: Xavier
authors.initials: X
authors.lastname: Declèves
mesh_terms: D001921:Brain / Q000166:cytology; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D055806:Microvessels / Q000166:cytology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon
keywords: Aryl hydrocarbon receptor; Blood-brain barrier; Pro-inflammatory cytokines; hCMEC/D3