title: Interleukin-10 is upregulated by nanomolar rosiglitazone treatment of mature dendritic cells and human CD4+ T cells.
abstract: Activators of peroxisome proliferator-activated receptor (PPAR)-gamma are anti-inflammatory and have been proposed as therapeutic agents for the treatment of Th1-type inflammatory diseases. We report that nanomolar concentrations of rosiglitazone enhance the production of IL-10 from activated human mature monocyte-derived dendritic cells. Also, rosiglitazone specifically induces the production of IL-10 from TCR-activated human CD4+ T cells and that this effect is PPAR-gamma-dependent. We also demonstrate for the first time the presence of a functional PPAR response element (PPRE) in the human IL-10 promoter region. Finally we show that rosiglitazone can induce IL-10 in combination with 1,25 alpha-dihydroxyvitamin D3 to a greater extent than each treatment alone. In summary our findings demonstrate that IL-10 is upregulated by nanomolar TZDs in immune cells, and this may, in part, be responsible for the potential anti-inflammatory effects of PPAR-gamma in humans.
authors.affiliation: Translational Medicine and Genetics, GlaxoSmithKline, ACCI, Addenbrooke's Hospital, Cambridge CB2 2GG, UK. Paul.W.Thompson@gsk.com
authors.forename: Paul W
authors.initials: PW
authors.lastname: Thompson
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Bayliffe
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Warren
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lamb
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics / Q000276:immunology