The MAP kinase pathway mediates transcytosis induced by TNF-α in an in vitro blood–brain barrier model

Authors

  • Florence Miller,

    1. Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique, Université d'Artois EA2465, Faculté des Sciences Jean Perrin, rue Jean Souvraz, 62307 Lens cedex, France
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  • Laurence Fenart,

    1. Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique, Université d'Artois EA2465, Faculté des Sciences Jean Perrin, rue Jean Souvraz, 62307 Lens cedex, France
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  • Valérie Landry,

    1. Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique, Université d'Artois EA2465, Faculté des Sciences Jean Perrin, rue Jean Souvraz, 62307 Lens cedex, France
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  • Caroline Coisne,

    1. Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique, Université d'Artois EA2465, Faculté des Sciences Jean Perrin, rue Jean Souvraz, 62307 Lens cedex, France
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  • Roméo Cecchelli,

    1. Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique, Université d'Artois EA2465, Faculté des Sciences Jean Perrin, rue Jean Souvraz, 62307 Lens cedex, France
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  • Marie-Pierre Dehouck,

    1. Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique, Université d'Artois EA2465, Faculté des Sciences Jean Perrin, rue Jean Souvraz, 62307 Lens cedex, France
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  • Valérie Buée-Scherrer

    1. Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique, Université d'Artois EA2465, Faculté des Sciences Jean Perrin, rue Jean Souvraz, 62307 Lens cedex, France
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Dr V. Buée-Scherrer, as above.
E-mail: valerie.buee@univ-artois.fr or valerie.buee-scherrer@lille.inserm.fr

Abstract

Cerebral capillary endothelial cells constitute the blood–brain barrier (BBB). In these highly specialized cells, transcellular transports rarely occur, and the presence of tight junctions between them leads to a low paracellular permeability. In order to understand the functions of this barrier, an in vitro model of the BBB has been developed and consists in a co-culture of primary cerebral capillary endothelial cells and glial cells. When these endothelial cells are subjected to an inflammatory agent, such as tumor necrosis factor-alpha (TNF-α), in vitro BBB permeability is increased, as indicated by the increase in holotransferrin transcytosis. However, no significant change in the paracellular permeability is observed. In order to understand the molecular mechanisms that underlie these transcytosis processes, we investigated the implication of the mitogen-activated protein kinase (MAPK) signalling pathway, as TNF-α is known to activate this kinase family. In the present study, an increase in the activation of p42–44 MAPK is observed after TNF-α treatment. Holotransferrin transcytosis as well as p42–44 MAPK activation are inhibited after addition of a p42–44 MAPK pathway inhibitor (UO126) during TNF-α challenge. These data suggest that the MAPK pathway is involved in the transcytosis regulation in endothelial cells from an in vitro BBB model.

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