Thompson Paul W, Bayliffe Andrew I, Warren Andrew P, Lamb Jonathan R
Translational Medicine and Genetics, GlaxoSmithKline, ACCI, Addenbrooke's Hospital, Cambridge CB2 2GG, UK.
Cytokine. 2007 Sep;39(3):184-91. doi: 10.1016/j.cyto.2007.07.191. Epub 2007 Sep 5.
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.
过氧化物酶体增殖物激活受体（PPAR）-γ激动剂具有抗炎作用，已被提议作为治疗Th1型炎症性疾病的药物。我们报告称，纳摩尔浓度的罗格列酮可增强活化的人成熟单核细胞来源的树突状细胞产生白细胞介素-10（IL-10）。此外，罗格列酮特异性诱导T细胞受体激活的人CD4+T细胞产生IL-10，且该效应依赖于PPAR-γ。我们还首次证明了人IL-10启动子区域存在功能性PPAR反应元件（PPRE）。最后，我们表明罗格列酮与1,25α-二羟基维生素D3联合诱导IL-10的程度比单独使用每种药物更大。总之，我们的研究结果表明，纳摩尔浓度的噻唑烷二酮类药物（TZDs）可上调免疫细胞中的IL-10，这可能部分解释了PPAR-γ在人体中的潜在抗炎作用。
