title: The PI3K/Akt pathway is required for LPS activation of microglial cells.
abstract: Upregulation of inflammatory responses in the brain is associated with a number of neurodegenerative diseases. Microglia are activated in neurodegenerative diseases, producing pro-inflammatory mediators. Critically, lipopolysaccharide (LPS)-induced microglial activation causes dopaminergic neurodegeneration in vitro and in vivo. The signaling mechanisms triggered by LPS to stimulate the release of pro-inflammatory mediators in microglial cells are still incompletely understood. To further explore the mechanisms of LPS-mediated inflammatory response of microglial cells, we studied the role of phosphatidylinositol 3-kinase (PI3K)/Akt signal transduction pathways known to be activated by toll-like receptor-4 signaling through LPS. In the current study, we report that the activation profile of LPS-induced pAkt activation preceded those of LPS-induced NF-κB activation, suggesting a role for PI3K/Akt in the pathway activation of NF-κB-dependent inflammatory responses of activated microglia. These results, providing the first evidence that PI3K dependent signaling is involved in the inflammatory responses of microglial cells following LPS stimulation, may be useful in preventing inflammatory based neurodegenerative processes.
authors.affiliation: Clinical Experimental Oncology Laboratory, National Cancer Centre, Bari Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Saponaro
authors.forename: Antonia
authors.initials: A
authors.lastname: Cianciulli
authors.forename: Rosa
authors.initials: R
authors.lastname: Calvello
authors.forename: Teresa
authors.initials: T
authors.lastname: Dragone
authors.forename: Francesco
authors.initials: F
authors.lastname: Iacobazzi
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Panaro
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D008070:Lipopolysaccharides / Q000633:toxicity*; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt