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The MAP kinase pathway mediates transcytosis induced by TNF-alpha in an in vitro blood-brain barrier model.
- Source :
-
The European journal of neuroscience [Eur J Neurosci] 2005 Aug; Vol. 22 (4), pp. 835-44. - Publication Year :
- 2005
-
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-alpha), 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-alpha is known to activate this kinase family. In the present study, an increase in the activation of p42-44 MAPK is observed after TNF-alpha treatment. Holotransferrin transcytosis as well as p42-44 MAPK activation are inhibited after addition of a p42-44 MAPK pathway inhibitor (UO126) during TNF-alpha challenge. These data suggest that the MAPK pathway is involved in the transcytosis regulation in endothelial cells from an in vitro BBB model.
- Subjects :
- Actins metabolism
Animals
Biological Transport drug effects
Biological Transport physiology
Blotting, Western methods
Butadienes pharmacology
Cattle
Cells, Cultured
Coculture Techniques methods
Drug Interactions
Endothelial Cells drug effects
Endothelium, Vascular cytology
Enzyme Inhibitors pharmacology
Immunohistochemistry methods
Mannitol pharmacology
Membrane Proteins metabolism
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 11 metabolism
Mitogen-Activated Protein Kinase 8 metabolism
Neuroglia drug effects
Nitriles pharmacology
Occludin
RNA, Messenger biosynthesis
Rats
Reverse Transcriptase Polymerase Chain Reaction methods
Blood-Brain Barrier drug effects
Blood-Brain Barrier metabolism
Mitogen-Activated Protein Kinases metabolism
Signal Transduction physiology
Tumor Necrosis Factor-alpha pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0953-816X
- Volume :
- 22
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The European journal of neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 16115207
- Full Text :
- https://doi.org/10.1111/j.1460-9568.2005.04273.x