title: Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis.
abstract: Toll receptors in Drosophila melanogaster function in morphogenesis and host defense. Mammalian orthologues of Toll, the Toll-like receptors (TLRs), have been studied extensively for their essential functions in controlling innate and adaptive immune responses. We report that TLR8 is dynamically expressed during mouse brain development and localizes to neurons and axons. Agonist stimulation of TLR8 in cultured cortical neurons causes inhibition of neurite outgrowth and induces apoptosis in a dissociable manner. Our evidence indicates that such TLR8-mediated neuronal responses do not involve the canonical TLR-NF-kappaB signaling pathway. These findings reveal novel functions for TLR8 in the mammalian nervous system that are distinct from the classical role of TLRs in immunity.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Ma
authors.forename: Jianxue
authors.initials: J
authors.lastname: Li
authors.forename: Isaac
authors.initials: I
authors.lastname: Chiu
authors.forename: Yawen
authors.initials: Y
authors.lastname: Wang
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Sloane
authors.forename: Jining
authors.initials: J
authors.lastname: Lü
authors.forename: Bela
authors.initials: B
authors.lastname: Kosaras
authors.forename: Richard L
authors.initials: RL
authors.lastname: Sidman
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Volpe
authors.forename: Timothy
authors.initials: T
authors.lastname: Vartanian
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018507:Gene Expression Regulation, Developmental; D051550:I-kappa B Kinase / Q000378:metabolism; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction; D051200:Toll-Like Receptor 8 / Q000235:genetics / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D051200:Toll-Like Receptor 8; D051550:I-kappa B Kinase