Expression and regulation of toll-like receptors in cerebral endothelial cells

Péter Nagyoszi, I. Wilhelm, Attila E. Farkas, Csilla Fazakas, Ngo Thi Khue Dung, János Haskó, I. Krizbai

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Cerebral endothelial cells - the principal components of the blood-brain barrier (BBB) - fulfill several important functions in the central nervous system (CNS). They form an active interface between blood and neuronal tissue and play a key role in the maintenance of the homeostasis of the CNS. Infections caused by different pathogens are often associated with systemic symptoms and may compromise the functional integrity of the BBB as well. In the mediation of the systemic effect of pathogens Toll-like receptors (TLRs) play a significant role. TLRs are a type of pattern recognition receptor and recognize molecules that are broadly shared by pathogens but distinguishable from host molecules. TLRs are broadly distributed on cells of the immune system and function as primary sensors of invading pathogens. There is also growing experimental evidence indicating that Toll-like receptors are expressed on different non-immune cell types as well, like epithelial or endothelial cells. Here we demonstrate the expression of TLR2, TLR3, TLR4 and TLR6 on rat and human cerebral endothelial cells. Oxidative stress significantly upregulated the expression of these receptors whereas TNF-alpha upregulated the expression of TLR2 and TLR3. Furthermore we have shown, that activation of TLR2/6 leads to an increased permeability which is accompanied by a downregulation of occludin and claudin-5 expression and disappearance of these tight junction proteins from the cell membrane. Changes in occludin expression and localization could be inhibited by the ERK1/2 inhibitor U0126. Our results suggest a significant role of the cerebral endothelium in mediation of the neural effects of different inflammatory processes.

Original languageEnglish
Pages (from-to)556-564
Number of pages9
JournalNeurochemistry International
Volume57
Issue number5
DOIs
Publication statusPublished - Nov 2010

Fingerprint

Toll-Like Receptors
Endothelial Cells
Occludin
Blood-Brain Barrier
Claudin-5
Central Nervous System
Tight Junction Proteins
Pattern Recognition Receptors
Cellular Structures
Endothelium
Immune System
Permeability
Oxidative Stress
Homeostasis
Down-Regulation
Tumor Necrosis Factor-alpha
Epithelial Cells
Maintenance
Cell Membrane
Infection

Keywords

  • Blood-brain barrier
  • Cerebral endothelial cells
  • Inflammation
  • Oxidative stress
  • Tight junction
  • TLR

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Expression and regulation of toll-like receptors in cerebral endothelial cells. / Nagyoszi, Péter; Wilhelm, I.; Farkas, Attila E.; Fazakas, Csilla; Dung, Ngo Thi Khue; Haskó, János; Krizbai, I.

In: Neurochemistry International, Vol. 57, No. 5, 11.2010, p. 556-564.

Research output: Contribution to journalArticle

Nagyoszi, Péter ; Wilhelm, I. ; Farkas, Attila E. ; Fazakas, Csilla ; Dung, Ngo Thi Khue ; Haskó, János ; Krizbai, I. / Expression and regulation of toll-like receptors in cerebral endothelial cells. In: Neurochemistry International. 2010 ; Vol. 57, No. 5. pp. 556-564.
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