title: IL-10 plays a pivotal role in anti-inflammatory effects of resveratrol in activated microglia cells.
abstract: The development of agents that can modulate microglial activation has been suggested as one potential strategy for the treatment or prevention of neurodegenerative diseases. Among these agents, resveratrol, with its anti-inflammatory action, has been described to have neuroprotective effects. In this paper we demonstrate that in LPS-stimulated microglia resveratrol pretreatment reduced, in a dose-dependent manner, pro-inflammatory cytokines IL-1β, TNF-α and IL-6 mRNA expression and increased the release of anti-inflammatory interleukin (IL)-10. Moreover, resveratrol pretreatment up-regulated the phosphorylated forms of JAK1 and STAT3, as well as suppressor of cytokine signaling (SOCS)3 protein expression in LPS activated cells, demonstrating that the JAK-STAT signaling pathway is involved in the anti-inflammatory effect exerted by resveratrol. By supplementing the cultures with an IL-10 neutralizing antibody (IL-10NA) we obtained the opposite effect. Taken together, these data allow us to conclude that the LPS-induced pro-inflammatory response in microglial cells can be markedly reduced by resveratrol, through IL-10 dependent up-regulation of SOCS3, requiring the JAK-STAT signaling pathway.
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Cianciulli
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Dragone
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of 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 Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, Lecce, Italy.
authors.forename: Dario Domenico
authors.initials: DD
authors.lastname: Lofrumento
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Italy. Electronic address: mariaantonietta.panaro@uniba.it.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Panaro
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D053613:Janus Kinase 1 / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000077185:Resveratrol; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D013267:Stilbenes; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1; D000077185:Resveratrol
keywords: IL-10; Inflammation; Microglia; Neurological diseases; Resveratrol