- Library Home /
- Search Collections /
- Open Collections /
- Browse Collections /
- UBC Faculty Research and Publications /
- Regulation of CCL2 and CCL3 expression in human brain...
Open Collections
UBC Faculty Research and Publications
Regulation of CCL2 and CCL3 expression in human brain endothelial cells by cytokines and lipopolysaccharide Chui, Ray; Dorovini-Zis, Katerina
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.
Item Metadata
Title |
Regulation of CCL2 and CCL3 expression in human brain endothelial cells by cytokines and lipopolysaccharide
|
Creator | |
Publisher |
BioMed Central
|
Date Issued |
2010-01-04
|
Description |
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.
|
Genre | |
Type | |
Language |
eng
|
Date Available |
2015-08-25
|
Provider |
Vancouver : University of British Columbia Library
|
Rights |
Attribution 4.0 International (CC BY 4.0)
|
DOI |
10.14288/1.0074629
|
URI | |
Affiliation | |
Citation |
Journal of Neuroinflammation. 2010 Jan 04;7(1):1
|
Publisher DOI |
10.1186/1742-2094-7-1
|
Peer Review Status |
Reviewed
|
Scholarly Level |
Faculty
|
Copyright Holder |
Chui and Dorovini-Zis.
|
Rights URI | |
Aggregated Source Repository |
DSpace
|
Item Media
Item Citations and Data
Rights
Attribution 4.0 International (CC BY 4.0)