title: The neurotoxic effect of astrocytes activated with toll-like receptor ligands.
abstract: Toll-like receptors (TLRs) are key molecules in the innate immune system in the central nervous system. Although astrocytes are believed to play physiological roles in regulating neuronal activity and synaptic transmission, activated astrocytes may also be toxic to neurons. Here, we show that the ligands for TLRs 2, 4, 5 and 6 induce neuronal cell death in neuron-astrocytes co-cultures through the production of reactive oxygen species (ROS). Inhibition of ROS production by NADPH oxidase inhibitor apocynin significantly suppresses neuronal cell death. ROS induced in astrocytes via TLRs may be involved in neuroinflammation and a therapeutic target for neurotoxicity by activated astrocytes.
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601 Japan.
authors.forename: Di
authors.initials: D
authors.lastname: Ma
authors.forename: Shijie
authors.initials: S
authors.lastname: Jin
authors.forename: Endong
authors.initials: E
authors.lastname: Li
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Doi
authors.forename: Bijiya
authors.initials: B
authors.lastname: Parajuli
authors.forename: Mariko
authors.initials: M
authors.lastname: Noda
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sonobe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizuno
authors.forename: Akio
authors.initials: A
authors.lastname: Suzumura
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002364:Caseins / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques; D004075:Diglycerides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D008024:Ligands; D055666:Lipopeptides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011066:Poly C / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000906:Antibodies; D002364:Caseins; D004075:Diglycerides; D004791:Enzyme Inhibitors; C460864:FSL-1 lipoprotein, synthetic; D006020:Glycopeptides; D053583:Interleukin-1beta; D008024:Ligands; D055666:Lipopeptides; D009573:Nitrites; D009842:Oligopeptides; C508075:Pam(3)CSK(4) peptide; D010455:Peptides; D011134:Polysaccharides; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C094310:kappa-caseinoglycopeptide; D011066:Poly C; D018698:Glutamic Acid; C056165:acetovanillone