title: Autophagy down regulates pro-inflammatory mediators in BV2 microglial cells and rescues both LPS and alpha-synuclein induced neuronal cell death.
abstract: Autophagy is a fundamental cellular homeostatic mechanism, whereby cells autodigest parts of their cytoplasm for removal or turnover. Neurodegenerative disorders are associated with autophagy dysregulation, and drugs modulating autophagy have been successful in several animal models. Microglial cells are phagocytes in the central nervous system (CNS) that become activated in pathological conditions and determine the fate of other neural cells. Here, we studied the effects of autophagy on the production of pro-inflammatory molecules in microglial cells and their effects on neuronal cells. We observed that both trehalose and rapamycin activate autophagy in BV2 microglial cells and down-regulate the production of pro-inflammatory cytokines and nitric oxide (NO), in response to LPS and alpha-synuclein. Autophagy also modulated the phosphorylation of p38 and ERK1/2 MAPKs in BV2 cells, which was required for NO production. These actions of autophagy modified the impact of microglial activation on neuronal cells, leading to suppression of neurotoxicity. Our results demonstrate a novel role for autophagy in the regulation of microglial cell activation and pro-inflammatory molecule secretion, which may be important for the control of inflammatory responses in the CNS and neurotoxicity.
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET). Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bussi
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET). Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Javier Maria
authors.initials: JM
authors.lastname: Peralta Ramos
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET). Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Arroyo
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET). Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Emilia A
authors.initials: EA
authors.lastname: Gaviglio
authors.affiliation: Departamento de Química Biológica, Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC, CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Gallea
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
authors.affiliation: Departamento de Química Biológica, Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC, CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Maria Soledad
authors.initials: MS
authors.lastname: Celej
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET). Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Pablo
authors.initials: P
authors.lastname: Iribarren
mesh_terms: D000818:Animals; D001343:Autophagy; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D009457:Neuroglia / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D015398:Signal Transduction; D051844:alpha-Synuclein / Q000633:toxicity*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D051844:alpha-Synuclein; D009569:Nitric Oxide