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Journal of Biomedicine and Biotechnology
Volume 2010, Article ID 307231, 10 pages
Research Article

TNF 𝛼 Induces Choroid Plexus Epithelial Cell Barrier Alterations by Apoptotic and Nonapoptotic Mechanisms

1Pediatric Infectious Diseases, Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
2Department of General Pediatrics, University Children's Hospital, Heinrich Heine University, Moorenstr. 5, 40225 Düsseldorf, Germany
3Interfaculty Institute for Biochemistry, University of Tübingen, Hoppe-Seyler-Str. 4, 72076 Tübingen, Germany
4Department of Biochemistry, Westfalian Wilhelms University, Wilhelm-Klemm-Str. 2, 48194 Münster, Germany

Received 10 July 2009; Revised 16 November 2009; Accepted 14 January 2010

Academic Editor: Amanda McCann

Copyright © 2010 Christian Schwerk et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The choroid plexus epithelium constitutes the structural basis of the blood-cerebrospinal fluid barrier. Since the cytokine TNF 𝛼 is markedly increased during inflammatory diseases in the blood and the central nervous system, we investigated by which mechanisms TNF 𝛼 induces barrier alteration in porcine choroid plexus epithelial cells. We found a dose-dependent decrease of transepithelial electrical resistance, increase of paracellular inulin-flux, and induction of histone-associated DNA fragmentation and caspase-3 activation after TNF 𝛼 stimulation. This response was strongly aggravated by the addition of cycloheximide and could partially be inhibited by the NF- 𝜅 B inhibitor CAPE, but most effectively by the pan-caspase-inhibitor zVAD-fmk and not by the JNK inhibitor SP600125. Partial loss of cell viability could also be attenuated by CAPE. Immunostaining showed cell condensation and nuclear binding of high-mobility group box 1 protein as a sign of apoptosis after TNF 𝛼 stimulation. Taken together our findings indicate that TNF 𝛼 compromises PCPEC barrier function by caspase and NF- 𝜅 B dependent mechanisms.