PMID- 25576658 OWN - NLM STAT- MEDLINE DCOM- 20151123 LR - 20181202 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 24 IP - 2 DP - 2015 Feb TI - IL-10 plays a pivotal role in anti-inflammatory effects of resveratrol in activated microglia cells. PG - 369-376 LID - S1567-5769(14)00513-X [pii] LID - 10.1016/j.intimp.2014.12.035 [doi] AB - 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-1beta, TNF-alpha 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. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Cianciulli, Antonia AU - Cianciulli A AD - Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Italy. FAU - Dragone, Teresa AU - Dragone T AD - Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Italy. FAU - Calvello, Rosa AU - Calvello R AD - Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Italy. FAU - Porro, Chiara AU - Porro C AD - Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy. FAU - Trotta, Teresa AU - Trotta T AD - Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy. FAU - Lofrumento, Dario Domenico AU - Lofrumento DD AD - Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, Lecce, Italy. FAU - Panaro, Maria Antonietta AU - Panaro MA AD - Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Italy. Electronic address: mariaantonietta.panaro@uniba.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150107 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Messenger) RN - 0 (STAT3 Transcription Factor) RN - 0 (Socs3 protein, mouse) RN - 0 (Stat3 protein, mouse) RN - 0 (Stilbenes) RN - 0 (Suppressor of Cytokine Signaling 3 Protein) RN - 0 (Suppressor of Cytokine Signaling Proteins) RN - EC 2.7.10.2 (Jak1 protein, mouse) RN - EC 2.7.10.2 (Janus Kinase 1) RN - Q369O8926L (Resveratrol) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Cell Line MH - Cytokines/genetics/*metabolism MH - Janus Kinase 1/metabolism MH - Lipopolysaccharides MH - Mice MH - Microglia/*drug effects/metabolism MH - RNA, Messenger/metabolism MH - Resveratrol MH - STAT3 Transcription Factor/metabolism MH - Stilbenes/*pharmacology MH - Suppressor of Cytokine Signaling 3 Protein MH - Suppressor of Cytokine Signaling Proteins/metabolism OTO - NOTNLM OT - IL-10 OT - Inflammation OT - Microglia OT - Neurological diseases OT - Resveratrol EDAT- 2015/01/13 06:00 MHDA- 2015/12/15 06:00 CRDT- 2015/01/11 06:00 PHST- 2014/10/06 00:00 [received] PHST- 2014/12/19 00:00 [revised] PHST- 2014/12/28 00:00 [accepted] PHST- 2015/01/11 06:00 [entrez] PHST- 2015/01/13 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] AID - S1567-5769(14)00513-X [pii] AID - 10.1016/j.intimp.2014.12.035 [doi] PST - ppublish SO - Int Immunopharmacol. 2015 Feb;24(2):369-376. doi: 10.1016/j.intimp.2014.12.035. Epub 2015 Jan 7.