Phorbol ester induced short- and long-term permeabilization of the blood-CSF barrier in vitro

被引:22
作者
Angelow, S [1 ]
Zeni, P [1 ]
Höhn, B [1 ]
Galla, HJ [1 ]
机构
[1] Univ Munster, Inst Biochem, D-48149 Munster, Germany
关键词
choroid plexus; in vitro model; phorbol ester; tight junction; cytoskeleton; MMP;
D O I
10.1016/j.brainres.2005.09.058
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Interconnected by tight junctions, the epithelial cells of the choroid plexus form a barrier separating the cerebrospinal fluid (CSF) from blood. Using an in vitro model based on porcine choroid plexus epithelial cells (PCPEC), we investigated the influence of PKC activating phorbol 12-myristate 13-acetate (PMA) on barrier properties and analyzed mechanisms involved :in the regulation of barrier tightness. Applied in concentrations of 5-25 nM, PMA induced a fast and lasting decrease of the transepithelial electrical resistance (TER), which could be blocked by rottlerin, indicating the involvement of PKC delta in signal transduction. The immediate impairment of barrier integrity was accompanied by dephosphorylation of occludin and formation of actin bundles. Moreover, in the presence of at least 25 nM PMA, changes of cell shape as well as discontinuities of tight junction strands were observed, suggesting the disruption of cell-cell contacts. Exposure to PMA for 1-2 days additionally induced down-regulation of claudin-2 and up-regulation of barrier modulating matrix metalloproteinase (MMP)-9, respectively. The results show that different interconnected mechanisms directly and indirectly targeting at the tight junctions are released by PMA contributing to the short-term and long-term decrease of TER and opening of the blood-CSF barrier in vitro. (C) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:168 / 179
页数:12
相关论文
共 34 条
[1]   Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells [J].
Amasheh, S ;
Meiri, N ;
Gitter, AH ;
Schöneberg, T ;
Mankertz, J ;
Schulzke, JD ;
Fromm, M .
JOURNAL OF CELL SCIENCE, 2002, 115 (24) :4969-4976
[2]   Functional characterisation of the active ascorbic acid transport into cerebrospinal fluid using primary cultured choroid plexus cells [J].
Angelow, S ;
Haselbach, M ;
Galla, HJ .
BRAIN RESEARCH, 2003, 988 (1-2) :105-113
[3]   Regulation of matrix metalloproteinases: An overview [J].
Chakraborti, S ;
Mandal, M ;
Das, S ;
Mandal, A ;
Chakraborti, T .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2003, 253 (1-2) :269-285
[4]  
Clarke H, 2000, J CELL SCI, V113, P3187
[5]   Regulation of airway tight junctions by proinflammatory cytokines [J].
Coyne, CB ;
Vanhook, MK ;
Gambling, TM ;
Carson, JL ;
Boucher, RC ;
Johnson, LG .
MOLECULAR BIOLOGY OF THE CELL, 2002, 13 (09) :3218-3234
[6]   Interleukin-6 causes endothelial barrier dysfunction via the protein kinase C pathway [J].
Desai, TR ;
Leeper, NJ ;
Hynes, KL ;
Gewertz, BL .
JOURNAL OF SURGICAL RESEARCH, 2002, 104 (02) :118-123
[7]   Divergent regulation by growth factors and cytokines of 95 kDa and 72 kDa gelatinases and tissue inhibitors of metalloproteinases-1, -2 and -3 in rabbit aortic smooth muscle cells [J].
Fabunmi, RP ;
Baker, AH ;
Murray, EJ ;
Booth, RFG ;
Newby, AC .
BIOCHEMICAL JOURNAL, 1996, 315 :335-342
[8]   Redistribution and phosphorylation of occludin during opening and resealing of tight junctions in cultured epithelial cells [J].
Farshori, P ;
Kachar, B .
JOURNAL OF MEMBRANE BIOLOGY, 1999, 170 (02) :147-156
[9]   Conversion of Zonulae occludentes from tight to leaky strand type by introducing claudin-2 into Madin-Darby canine kidney I cells [J].
Furuse, M ;
Furuse, K ;
Sasaki, H ;
Tsukita, S .
JOURNAL OF CELL BIOLOGY, 2001, 153 (02) :263-272
[10]  
GOLDBERG GI, 1992, J BIOL CHEM, V267, P4583