title: PI3k/Akt signalling pathway plays a crucial role in the anti-inflammatory effects of curcumin in LPS-activated microglia.
abstract: Microglia are resident macrophages in the central nervous system (CNS) deputed to defend against pathogens. Persistent or acute inflammation of microglia leads to CNS disorders, so regulation of pro-inflammatory responses of microglial cells is thought to be a promising therapeutic strategy to attenuate abnormal inflammatory responses observed in neurodegenerative disease. We hypothesized that curcumin supplementation could reduce the inflammatory responses of activated microglial cells modulating PI3K/Akt pathway. Different curcumin concentrations were administered as BV-2 microglia pre-treatment 1h prior to LPS stimulation. Nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression were determined by Griess reagent and western blotting, respectively. Inflammatory cytokines release was evaluated by ELISA and qRT-PCR. PI3K/Akt expression was analyzed by western blotting analysis. Curcumin significantly attenuated, in a dose-dependent manner, LPS-induced release of NO and pro-inflammatory cytokines, as well as iNOS expression. Interestingly, curcumin was able to reduce, again in a dose-dependent manner, PI3K/Akt phosphorylation as well as NF-κB activation in LPS-activated microglial cells. Overall these results suggest that curcumin plays an important role in the attenuation of LPS-induced inflammatory responses in microglial cells and that the mechanisms involve down-regulation of the PI3K/Akt signalling.
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy. Electronic address: antonia.cianciulli@uniba.it.
authors.forename: Antonia
authors.initials: A
authors.lastname: Cianciulli
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Calvello
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Porro
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Trotta
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Salvatore
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Panaro
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D003474:Curcumin
keywords: Curcumin; Cytokines; Inflammation; Microglia; Nitric oxide; PI3K/Akt