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首页> 外文期刊>BMC Rheumatology >Resveratrol displays anti-inflammatory properties in an ex vivo model of immune mediated inflammatory arthritis
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Resveratrol displays anti-inflammatory properties in an ex vivo model of immune mediated inflammatory arthritis

机译:白藜芦醇在免疫介导的炎性关节炎的离体模型中显示抗炎特性

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Resveratrol is a natural polyphenol found in berries, roots and wine that is well known to have anti-inflammatory and anti-oxidative properties. The anti-inflammatory effect has been reported for both immune cells and connective tissues, but only few studies have investigated effects on immune mediated inflammatory arthritis. None of which have studied this effect when combining resveratrol with methotrexate or adalimumab, two major drugs in the treatment of immune mediated inflammatory arthritis. We therefore aimed to investigate the anti-inflammatory effect of resveratrol alone and in combination with methotrexate or adalimumab in ex vivo models of immune mediated inflammatory arthritis. We furthermore aimed to describe any variations in this effect based on disease activity and cellular composition of the synovial fluid infiltrate. Synovial fluid mononuclear cells from patients with rheumatoid arthritis (n = 7) and spondyloarthritis (n = 7) were cultured for either 48 h or 21 days. In both models, synovial fluid mononuclear cells were treated with resveratrol alone or in combination with methotrexate or adalimumab. Monocyte chemoattractant protein 1, matrix metalloproteinase 3 and tartrate resistant acidic phosphatase were measured to quantify inflammation, enzymatic degradation and osteoclast differentiation, respectively. Resveratrol reduced monocyte chemoattractant protein 1 production by synovial fluid mononuclear cells significantly (p = 0.005) compared to untreated controls. The effect of resveratrol was greatest in cultures from patients with low disease activity, i.e. DAS28CRP ≤ 3.2 (p = 0.022), and in cultures dominated by lymphocytes (p = 0.03). Further, the combination of methotrexate and resveratrol significantly reduced monocyte chemoattractant protein 1 levels compared with methotrexate alone in cultures from patients with low disease activity (p = 0.016), and in cultures with high lymphocyte count (p = 0.011). Resveratrol did not significantly affect matrix metalloproteinase 3 and tartrate resistant acidic phosphatase production. Resveratrol has anti-inflammatory properties in our ex vivo model of immune mediated inflammatory arthritis. Results show an additive effect of resveratrol, when combined with methotrexate in samples dominated by lymphocytes and samples from patients with low disease activity. This suggests further investigations in vitro and whether this effect may also be present in a clinical setting.
机译:白藜芦醇是存在于浆果,根和酒中的天然多酚,众所周知具有抗炎和抗氧化特性。已经报道了免疫细胞和结缔组织的抗炎作用,但是只有很少的研究研究了对免疫介导的炎性关节炎的作用。当白藜芦醇与甲氨蝶呤或阿达木单抗(两种用于治疗免疫介导的炎性关节炎的主要药物)联合使用时,没有人研究过这种作用。因此,我们旨在研究白藜芦醇单独和与甲氨蝶呤或阿达木单抗联合在免疫介导的炎性关节炎的离体模型中的抗炎作用。我们还旨在描述基于疾病活动和滑液浸润的细胞组成的这种效应的任何变化。将类风湿关节炎(n = 7)和脊椎关节炎(n = 7)患者的滑液单核细胞培养48小时或21天。在这两种模型中,单独用白藜芦醇或与甲氨蝶呤或阿达木单抗联合治疗滑液单核细胞。测量单核细胞趋化蛋白1,基质金属蛋白酶3和酒石酸抗性酸性磷酸酶,以分别量化炎症,酶促降解和破骨细胞分化。与未处理的对照组相比,白藜芦醇显着降低了滑液单核细胞产生的单核细胞趋化蛋白1的产生(p = 0.005)。白藜芦醇的作用在疾病活动低的患者的培养物中最大,即DAS28CRP≤3.2(p = 0.022),在以淋巴细胞为主的培养物中(p = 0.03)。此外,与甲氨蝶呤单独使用相比,甲氨蝶呤和白藜芦醇的组合显着降低了疾病活动性较低患者的培养物中的单核细胞趋化蛋白1水平(p = 0.016)和淋巴细胞计数较高的培养物中(p = 0.011)。白藜芦醇没有显着影响基质金属蛋白酶3和酒石酸盐抗性酸性磷酸酶的生产。白藜芦醇在我们的免疫介导的炎性关节炎的离体模型中具有抗炎特性。结果显示,白藜芦醇与甲氨蝶呤联用在淋巴细胞占主导地位的样品和疾病活动低的患者样品中时,具有加和作用。这提示了进一步的体外研究,以及这种作用是否也可能存在于临床环境中。

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