Title
Identification of soluble CD14 as an endogenous agonist for toll-like receptor 2 on human astrocytes by genome-scale functional screening of glial cell derived proteins
Author
Bsibsi, M.
Bajramovic, J.J.
van Duijvenvoorden, E.
Persoon, C.
Ravid, R.
van Noort, J.M.
Vogt, M.H.J.
TNO Kwaliteit van Leven
Publication year
2007
Abstract
Human astrocytes express a limited repertoire of Toll-like receptor (TLR) family members including TLR1-4, which are expressed on the cell surface. Also, TLR3 but not TLR4 activation on astrocytes induces expression of several factors involved in neuroprotection and down-regulation of inflammation rather than in the onset of traditional pro-inflammatory reactions. The notion that astrocyte TLR may thus play a role not only in host defense but also in tissue repair responses prompted us to examine the possibility that endogenous TLR agonists could be expressed in the human central nervous system to regulate the apparently dual astrocyte functions during trauma or inflammation. As a potential source of endogenous agonists, a cDNA library derived from several human brain tumor cell lines was used. Gene pools of this library were transfected into COS-7 cells and the expression products were screened for their ability to induce TLR activation in human primary astrocytes. The screening resulted in the identification of soluble CD14. By using a panel of TLR-transfected HEK293 cells, we found that signaling by soluble CD14 was TLR2 dependent. Moreover, the CD14-triggered TLR2-mediated response in astrocytes lead to the production of CXCL8, IL-6, and IL12p40, whereas typical TLR-induced pro-inflammatory cytokines, like TNF-α and IL-1β, were not produced at detectable levels. In conclusion, our data indicate that apart from its well-known ability to act as a co-receptor for TLR-dependent signaling by peptidoglycans or LPS, soluble CD14 can also act as a direct agonist for TLR2. ©2007 Wiley-Liss, Inc.
Subject
Biomedical Research
CD14
Functional genomics
Toll-like receptors
CD14 antigen
complementary DNA
interleukin 12p40
interleukin 1beta
interleukin 6
interleukin 8
soluble cd14 antigen
toll like receptor 2
tumor necrosis factor alpha
animal cell
article
astrocyte
brain tumor
cell stimulation
controlled study
cytokine release
DNA library
gene pool
genetic screening
genetic transfection
genome
human
human cell
human tissue
microglia
nonhuman
priority journal
protein synthesis
receptor upregulation
tumor cell line
Adult
Amino Acid Sequence
Animals
Antigens, CD14
Astrocytes
Base Sequence
Cells, Cultured
Cercopithecus aethiops
COS Cells
DNA, Complementary
Gene Expression Profiling
Genomic Library
Humans
Interleukin-12 Subunit p40
Interleukin-6
Interleukin-8
Interleukins
Macaca mulatta
Microglia
Molecular Sequence Data
Signal Transduction
Toll-Like Receptor 2
To reference this document use:
http://resolver.tudelft.nl/uuid:7403af58-5f18-4df5-bdc5-e6f6c5216d97
DOI
https://doi.org/10.1002/glia.20473
TNO identifier
239912
ISSN
0894-1491
Source
GLIA, 55 (5), 473-482
Document type
article