Print Email Facebook Twitter 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 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 ResearchCD14Functional genomicsToll-like receptorsCD14 antigencomplementary DNAinterleukin 12p40interleukin 1betainterleukin 6interleukin 8soluble cd14 antigentoll like receptor 2tumor necrosis factor alphaanimal cellarticleastrocytebrain tumorcell stimulationcontrolled studycytokine releaseDNA librarygene poolgenetic screeninggenetic transfectiongenomehumanhuman cellhuman tissuemicroglianonhumanpriority journalprotein synthesisreceptor upregulationtumor cell lineAdultAmino Acid SequenceAnimalsAntigens, CD14AstrocytesBase SequenceCells, CulturedCercopithecus aethiopsCOS CellsDNA, ComplementaryGene Expression ProfilingGenomic LibraryHumansInterleukin-12 Subunit p40Interleukin-6Interleukin-8InterleukinsMacaca mulattaMicrogliaMolecular Sequence DataSignal TransductionToll-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 Files To receive the publication files, please send an e-mail request to TNO Library.