%0 Journal Article %1 Iliev2004 %A Iliev, A. I. %A Stringaris, A. K. %A Nau, R. %A Neumann, H. %D 2004 %J FASEB J %K 9 Biological Cell Cerebral Cortex/drug CpG Cultured DNA DNA-Binding DNA/genetics/toxicity Factor-alpha/metabolism Hippocampus/drug Islands/genetics Methylation Microglia/cytology/drug Models, Necrosis Neurites/drug Neurons/drug Nitric Oligonucleotides/genetics/toxicity Oxide/metabolism Receptor Surface/*metabolism Toll-Like Tumor effects/*metabolism effects/*metabolism/*pathology effects/metabolism/pathology effects/pathology Proteins/metabolism %N 2 %P 412-4 %T Neuronal injury mediated via stimulation of microglial toll-like receptor-9 (TLR9) %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14688201 %V 18 %X Innate immune cells express toll-like receptor-9 (TLR9) and respond to unmethylated, CG dinucleotide motif-rich DNA released from bacteria during infection or endogenous cells during autoimmune tissue injury. Oligonucleotides containing CG dinucleotide (CpG-DNA) mimic the effect of unmethylated DNA and stimulate TLR9. CpG-DNA was cytotoxic to neurons in organotypic brain cultures. Neurotoxicity of CpG-DNA was mediated via microglial cells and started primarily from neurites as determined by time-lapse imaging of enhanced green fluorescent protein (EGFP)-transfected neurons. Cultured brain microglial cells expressed TLR9 and responded to CpG-DNA by production of the inflammatory mediators nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). Blockade of NO synthase and TNF-alpha prevented damage of neurites and neurotoxicity of CpG-DNA. The data suggest that stimulation of microglia via TLR9 and subsequent release of NO and TNF-alpha is a major source of neurotoxicity in bacterial and autoimmune brain tissue injury.

@article{Iliev2004, abstract = {Innate immune cells express toll-like receptor-9 (TLR9) and respond to unmethylated, CG dinucleotide motif-rich DNA released from bacteria during infection or endogenous cells during autoimmune tissue injury. Oligonucleotides containing CG dinucleotide (CpG-DNA) mimic the effect of unmethylated DNA and stimulate TLR9. CpG-DNA was cytotoxic to neurons in organotypic brain cultures. Neurotoxicity of CpG-DNA was mediated via microglial cells and started primarily from neurites as determined by time-lapse imaging of enhanced green fluorescent protein (EGFP)-transfected neurons. Cultured brain microglial cells expressed TLR9 and responded to CpG-DNA by production of the inflammatory mediators nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). Blockade of NO synthase and TNF-alpha prevented damage of neurites and neurotoxicity of CpG-DNA. The data suggest that stimulation of microglia via TLR9 and subsequent release of NO and TNF-alpha is a major source of neurotoxicity in bacterial and autoimmune brain tissue injury.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Iliev, A. I. and Stringaris, A. K. and Nau, R. and Neumann, H.}, biburl = {https://www.bibsonomy.org/bibtex/252c8ea09c133d59dcba345aeb9f87813/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {f4c3252f198a5c0454dbd7a798c12c44}, intrahash = {52c8ea09c133d59dcba345aeb9f87813}, issn = {1530-6860 (Electronic) 1530-6860 (Linking)}, journal = {FASEB J}, keywords = {9 Biological Cell Cerebral Cortex/drug CpG Cultured DNA DNA-Binding DNA/genetics/toxicity Factor-alpha/metabolism Hippocampus/drug Islands/genetics Methylation Microglia/cytology/drug Models, Necrosis Neurites/drug Neurons/drug Nitric Oligonucleotides/genetics/toxicity Oxide/metabolism Receptor Surface/*metabolism Toll-Like Tumor effects/*metabolism effects/*metabolism/*pathology effects/metabolism/pathology effects/pathology Proteins/metabolism}, month = Feb, note = {Iliev, Asparouh I Stringaris, Argyrios K Nau, Roland Neumann, Harald In Vitro United States The FASEB journal : official publication of the Federation of American Societies for Experimental Biology FASEB J. 2004 Feb;18(2):412-4. Epub 2003 Dec 19.}, number = 2, pages = {412-4}, shorttitle = {Neuronal injury mediated via stimulation of microglial toll-like receptor-9 (TLR9)}, timestamp = {2010-12-14T18:21:42.000+0100}, title = {Neuronal injury mediated via stimulation of microglial toll-like receptor-9 (TLR9)}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14688201}, volume = 18, year = 2004 }