Inhibitory effects of lutein on endotoxin-induced uveitis in Lewis rats
Inhibitory effects of lutein on endotoxin-induced uveitis in Lewis rats
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DOI：
10.1167/iovs.05-1429
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发表时间：
2006-06-01
影响因子：
4.4
通讯作者：
Ohno, Shigeaki
中科院分区：
文献类型：
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作者：
Jin, Xue-Hai;Ohgami, Kazubiro;Ohno, Shigeaki
目的。叶黄素以高浓度沉积在人眼的黄斑和晶状体中，因其对年龄相关性黄斑变性和白内障等眼部疾病的有益作用而被称为护眼营养素。本研究的目的是探讨叶黄素对大鼠内毒素性葡萄膜炎（EIU）的影响。通过皮下注射200μg脂多糖在雄性Lewis大鼠中诱导EIU。在LPS治疗前30分钟、同时和治疗后30分钟静脉注射叶黄素或地塞米松。注射LPS后24小时采集房水，测定房水中浸润细胞数、蛋白浓度以及一氧化氮（NO）、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、前列腺素（PG）-E2、单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎症蛋白（MIP）-2的水平。使用针对活化核因子 (NF)-κ B 的单克隆抗体进行免疫组织化学染色，以评估叶黄素对大鼠虹膜睫状体 (ICB) 中 NF-κ B 活化的影响。在叶黄素存在或不存在的情况下，用 LPS 刺激小鼠巨噬细胞系（RAW264.7 细胞）。通过Western印迹分析诱导型NO合酶(iNOS)、环氧合酶-2(COX-2)的表达和抑制剂κB(IκB)的降解。结果。叶黄素以剂量依赖性方式抑制 EIU 的发展。 100mg/kg叶黄素的抗炎作用与1mg/kg地塞米松一样强。叶黄素治疗降低了房水中 NO、TNF-α、IL-6、PGE2、MCP-1 和 MIP-2 的浓度。叶黄素还抑制 ICB 中 NF-kappa B 的激活以及 RAW 细胞中 iNOS 和 COX-2 的表达以及 I kappa B 的降解。结论。这些发现表明，叶黄素通过抑制 NF-κ B 依赖性信号通路以及随后促炎介质的产生，对 EIU 具有抗炎作用。
PURPOSE. Lutein deposits in the macula and lens of human eyes with high concentration and is well known as an eye-protective nutrient for its beneficial effects on eye disease such as age-related macular degeneration and cataract. The purpose of the present study was to investigate the effects of lutein on endotoxin-induced uveitis (EIU) in rats.METHODS. EIU was induced in male Lewis rats by subcutaneous injection of 200 mu g lipopolysaccharide. Lutein or dexamethasone was administered intravenously at 30 minutes before, at the same time as, and at 30 minutes after LPS treatment. The aqueous humor was collected at 24 hours after LPS injection, the number of infiltrating cells, the protein concentration, and the levels of nitric oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, prostaglandin (PG)-E2, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-2 in the aqueous humor were determined. Immunohistochemical staining with a monoclonal antibody against activated nuclear factor (NF)-kappa B was performed to evaluate the effect of lutein on NF-kappa B activation in the iris-ciliary body (ICB) of rats. A mouse macrophage cell line (RAW264.7 cells) was stimulated with LPS, in the presence or absence of lutein. Expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and degradation of inhibitor kappa B (I kappa B) were analyzed by Western blot analysis.RESULTS. Lutein suppressed the development of EIU in a dose-dependent fashion. The anti-inflammatory effect of 100 mg/kg lutein was as strong as that of I mg/kg dexamethasone. Treatment with lutein reduced the concentrations of NO, TNF-alpha, IL-6, PGE2, MCP-1, and MIP-2 in aqueous humor. Lutein also suppressed the activation of NF-kappa B in the ICB as well as iNOS and COX-2 expression and I kappa B degradation in RAW cells. CCONCLUSIONS. These findings indicate that lutein has anti-inflammatory effects on EIU by inhibiting the NF-kappa B dependent signaling pathway and the subsequent production of proinflammatory mediators.