Print Email Facebook Twitter Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators Title Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators Author Bsibsi, M. Persoon-Deen, C. Verwer, R.W.H. Meeuwsen, S. Ravid, R. van Noort, J.M. TNO Kwaliteit van Leven Publication year 2006 Abstract Toll-like receptors (TLRs) are innate immunity receptors that are expressed on a wide range of cell types, including CNS glial cells. In general, TLR engagement by specific sets of microbial ligands triggers production of pro-inflammatory factors and enhances antigen-presenting cell functions. The functional roles of TLR in the CNS, however, are still poorly understood. While adult human astrocytes in culture dominantly express TLR4, they display a strikingly strong and selective induction of TLR3 when activated by pro-inflammatory cytokines, TLR3 or TLR4 agonists, or oxidative stress. Gene profiling analysis of the astrocyte response to either TLR3 or TLR4 activation revealed that TLR3, but not TLR4, induces expression of a range of neuroprotective mediators and several other molecules that regulate cellular growth, differentiation, and migration. Also, TLR3 triggered enhanced production of anti-inflammatory cytokines including interleukin-9 (IL-9), IL-10, and IL-11 and downregulation of the p40 subunit of IL-12 and IL-23. The collective TLR3-induced products were found in functional assays to inhibit astrocyte growth, promote human endothelial cell growth, and importantly, to enhance neuronal survival in organotypic human brain slice cultures. Together, our data indicate that TLR3 is induced on human astrocytes upon inflammation and when activated, mediates a comprehensive neuroprotective response rather than a polarized pro-inflammatory reaction. © 2006 Wiley-Liss, Inc. Chemicals / CAS: interleukin 12, 138415-13-1; polyinosinic polycytidylic acid, 24939-03-5, 26301-44-0; toll like receptor 4, 203811-83-0; Cytokines; Growth Inhibitors; Growth Substances; Interleukins; Neuroprotective Agents; TLR3 protein, human; TLR4 protein, human; Toll-Like Receptor 3; Toll-Like Receptor 4 Subject BiologyBiomedical ResearchAstrocytesInflammationNeuroprotectionToll-like receptorsinterleukin 10interleukin 12interleukin 23interleukin 9lipopolysaccharidepolyinosinic polycytidylic acidprotein p40cell differentiationcell growthcell migrationcontrolled studygene inductiongenetic analysishuman cellhuman tissuenerve cellneuroprotectionnucleotide sequenceoxidative stressprotein expressionprotein inductionunindexed sequenceAgedAged, 80 and overAstrocytesCell SurvivalCells, CulturedCytokinesCytoprotectionDown-RegulationEncephalitisEndothelial CellsFemaleGliosisGrowth InhibitorsGrowth SubstancesHumansInterleukinsMaleNeuroprotective AgentsToll-Like Receptor 3Toll-Like Receptor 4Up-Regulation To reference this document use: http://resolver.tudelft.nl/uuid:86c154ff-2336-43eb-8c81-b9d5111dc356 DOI https://doi.org/10.1002/glia.20328 TNO identifier 239257 ISSN 0894-1491 Source GLIA, 53 (7), 688-695 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.