Expression and Localization of Claudins-3 and -12 in Transformed Human Brain Endothelium

Overview

Journal Fluids Barriers CNS

Publisher Biomed Central

Date 2012 Mar 1

PMID 22373538

Citations 23

Authors

Anja Schrade

Hadassah Sade

Pierre-Olivier Couraud

Ignacio A Romero

Babette B Weksler

Jens Niewoehner

Affiliations

Soon will be listed here.

Abstract

Background: The aim of this study was to characterize the hCMEC/D3 cell line, an in vitro model of the human Blood Brain Barrier (BBB) for the expression of brain endothelial specific claudins-3 and -12.

Findings: hCMEC/D3 cells express claudins-3 and -12. Claudin-3 is distinctly localized to the TJ whereas claudin -12 is observed in the perinuclear region and completely absent from TJs. We show that the expression of both proteins is lost in cell passage numbers where the BBB properties are no longer fully conserved. Expression and localization of claudin-3 is not modulated by simvastatin shown to improve barrier function in vitro and also recommended for routine hCMEC/D3 culture.

Conclusions: These results support conservation of claudin-3 and -12 expression in the hCMEC/D3 cell line and make claudin-3 a potential marker for BBB characteristics in vitro.

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References

Mahajan S, Aalinkeel R, Sykes D, Reynolds J, Bindukumar B, Adal A . Methamphetamine alters blood brain barrier permeability via the modulation of tight junction expression: Implication for HIV-1 neuropathogenesis in the context of drug abuse. Brain Res. 2008; 1203:133-48. PMC: 2826119. DOI: 10.1016/j.brainres.2008.01.093. View

Weksler B, Subileau E, Perriere N, Charneau P, Holloway K, Leveque M . Blood-brain barrier-specific properties of a human adult brain endothelial cell line. FASEB J. 2005; 19(13):1872-4. DOI: 10.1096/fj.04-3458fje. View

Coisne C, Dehouck L, Faveeuw C, Delplace Y, Miller F, Landry C . Mouse syngenic in vitro blood-brain barrier model: a new tool to examine inflammatory events in cerebral endothelium. Lab Invest. 2005; 85(6):734-46. DOI: 10.1038/labinvest.3700281. View

Liebner S, Fischmann A, Rascher G, Duffner F, Grote E, Kalbacher H . Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme. Acta Neuropathol. 2000; 100(3):323-31. DOI: 10.1007/s004010000180. View

Belanger M, Asashima T, Ohtsuki S, Yamaguchi H, Ito S, Terasaki T . Hyperammonemia induces transport of taurine and creatine and suppresses claudin-12 gene expression in brain capillary endothelial cells in vitro. Neurochem Int. 2006; 50(1):95-101. DOI: 10.1016/j.neuint.2006.07.005. View

Nitta T, Hata M, Gotoh S, Seo Y, Sasaki H, Hashimoto N . Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol. 2003; 161(3):653-60. PMC: 2172943. DOI: 10.1083/jcb.200302070. View

Wolburg H, Wolburg-Buchholz K, Kraus J, Rascher-Eggstein G, Liebner S, Hamm S . Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme. Acta Neuropathol. 2003; 105(6):586-92. DOI: 10.1007/s00401-003-0688-z. View

Perriere N, Demeuse P, Garcia E, Regina A, Debray M, Andreux J . Puromycin-based purification of rat brain capillary endothelial cell cultures. Effect on the expression of blood-brain barrier-specific properties. J Neurochem. 2005; 93(2):279-89. DOI: 10.1111/j.1471-4159.2004.03020.x. View

Morita K, Sasaki H, Furuse M, Tsukita S . Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol. 1999; 147(1):185-94. PMC: 2164984. DOI: 10.1083/jcb.147.1.185. View

10.

Markoutsa E, Pampalakis G, Niarakis A, Romero I, Weksler B, Couraud P . Uptake and permeability studies of BBB-targeting immunoliposomes using the hCMEC/D3 cell line. Eur J Pharm Biopharm. 2010; 77(2):265-74. DOI: 10.1016/j.ejpb.2010.11.015. View

11.

Ifergan I, Wosik K, Cayrol R, Kebir H, Auger C, Bernard M . Statins reduce human blood-brain barrier permeability and restrict leukocyte migration: relevance to multiple sclerosis. Ann Neurol. 2006; 60(1):45-55. DOI: 10.1002/ana.20875. View

12.

Buttmann M, Lorenz A, Weishaupt A, Rieckmann P . Atorvastatin partially prevents an inflammatory barrier breakdown of cultured human brain endothelial cells at a pharmacologically relevant concentration. J Neurochem. 2007; 102(4):1001-8. DOI: 10.1111/j.1471-4159.2007.04563.x. View

13.

Forster C, Burek M, Romero I, Weksler B, Couraud P, Drenckhahn D . Differential effects of hydrocortisone and TNFalpha on tight junction proteins in an in vitro model of the human blood-brain barrier. J Physiol. 2008; 586(7):1937-49. PMC: 2375735. DOI: 10.1113/jphysiol.2007.146852. View