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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2010

Open Access 01-12-2010 | Research

Regulation of CCL2 and CCL3 expression in human brain endothelial cells by cytokines and lipopolysaccharide

Authors: Ray Chui, Katerina Dorovini-Zis

Published in: Journal of Neuroinflammation | Issue 1/2010

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Abstract

Background

Chemokines are emerging as important mediators of CNS inflammation capable of activating leukocyte integrins and directing the migration of leukocyte subsets to sites of antigenic challenge. In this study we investigated the expression, release and binding of CCL2 (MCP-1) and CCL3 (MIP-1α) in an in vitro model of the human blood-brain barrier.

Methods

The kinetics of expression and cytokine upregulation and release of the β-chemokines CCL2 and CCL3 were studied by immunocytochemistry and enzyme-linked immunosorbent assay in primary cultures of human brain microvessel endothelial cells (HBMEC). In addition, the differential binding of these chemokines to the basal and apical endothelial cell surfaces was assessed by immunoelectron microscopy.

Results

Untreated HBMEC synthesize and release low levels of CCL2. CCL3 is minimally expressed, but not released by resting HBMEC. Treatment with TNF-α, IL-1β, LPS and a combination of TNF-α and IFN-γ, but not IFN-γ alone, significantly upregulated the expression and release of both chemokines in a time-dependent manner. The released CCL2 and CCL3 bound to the apical and basal endothelial surfaces, respectively. This distribution was reversed in cytokine-activated HBMEC resulting in a predominantly basal localization of CCL2 and apical distribution of CCL3.

Conclusions

Since cerebral endothelial cells are the first resident CNS cells to contact circulating leukocytes, expression, release and presentation of CCL2 and CCL3 on cerebral endothelium suggests an important role for these chemokines in regulating the trafficking of inflammatory cells across the BBB in CNS inflammation.
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Metadata
Title
Regulation of CCL2 and CCL3 expression in human brain endothelial cells by cytokines and lipopolysaccharide
Authors
Ray Chui
Katerina Dorovini-Zis
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2010
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-7-1

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