Lutein or Zeaxanthin Supplementation Suppresses Inflammatory Responses in Retinal Pigment Epithelial Cells and Macrophages
Lutein or Zeaxanthin Supplementation Suppresses Inflammatory Responses in Retinal Pigment Epithelial Cells and Macrophages
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DOI：
10.1007/978-1-4614-0631-0_7
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Shang, Fu
中科院分区：
文献类型：
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作者：
Bian, Qingning;Qin, Tingyu;Shang, Fu
最近的研究表明，过度的炎症反应与年龄相关性黄斑变性(AMD)的发病机制有关。流行病学研究表明，膳食中叶黄素和玉米黄质的摄入与全身性炎症和AMD的风险成反比。这项工作的目的是直接确定补充叶黄素和玉米黄质对眼部和全身炎症反应的影响。将ARPE-19细胞和原代小鼠巨噬细胞分别加入0、1和10μM叶黄素或玉米黄质培养1~3天，然后在新鲜培养液中用脂多糖刺激8h，用ELISA法测定培养上清液中IL-6、IL-8和肿瘤坏死因子α的水平，以此作为炎症反应的指标。为检测叶黄素/玉米黄质在体内的抗炎作用，对C57BL小鼠饲喂含0、0.02%和0.1%叶黄素或玉米黄质的饲料3个月。从腹膜分离巨噬细胞，加入内毒素培养16h，测定培养上清液中IL-6和肿瘤坏死因子α的水平。培养的RPE即使在无内毒素的情况下也能产生较高水平的IL-6和IL-8，而静息状态下巨噬细胞分泌的IL-6和TNF-1几乎检测不到。用脂多糖处理视网膜色素上皮和巨噬细胞后，IL-6、IL-8和肿瘤坏死因子α的产生显著增加。补充叶黄素可抑制脂多糖刺激的RPE和巨噬细胞中这些炎症介质的产生。这些抑制作用呈剂量依赖关系。在没有内毒素刺激的情况下，向培养的RPE中添加叶黄素也能抑制IL-6和IL-8的产生。此外，添加叶黄素的小鼠巨噬细胞在内毒素刺激下产生的IL-6和肿瘤坏死因子α较少，且抑制作用呈剂量依赖关系。补充玉米黄质可抑制IL-8的产生，但不能抑制IL-6的产生。这些数据表明，叶黄素和玉米黄质具有抗炎作用，增加饮食中叶黄素或玉米黄质的摄入量可能通过调节眼部和全身炎症来降低AMD的风险。
Recent studies indicate that an excessive inflammatory response is etiologically related to the pathogenesis of age-related macular degeneration (AMD). Epidemiologic studies suggest that dietary lutein and zeaxanthin intake is inversely associated systemic inflammation and risk for AMD. The objective of this work is to directly determine the effects of lutein and zeaxanthin supplementation on ocular and systemic inflammatory response. ARPE-19 cells and primary murine macrophages were cultured in the presence of 0, 1 and 10 μM lutein or zeaxanthin for 1–3 days and then stimulated with lipopolysaccharide (LPS) in fresh medium for 8 h. Levels of IL-6, IL-8 and TNFα in the medium were determined by ELISA and used as indicators of inflammatory response. To test the anti-inflammatory effects of lutein/zeaxanthin in vivo, C57BL mice were fed diets containing 0, 0.02%, and 0.1% lutein or zeaxanthin for 3 months. Macrophages were isolated from peritonea and cultured in the presence of LPS for 16 h. Levels of IL-6 and TNFα in the medium were determined. Cultured RPE produced relatively high levels of IL-6 and IL-8 even in the absence of LPS, but levels of IL-6 and TNF< secreted by macrophages in resting state were barely detectable. Treatment of RPE and macrophages with LPS resulted in a dramatic increase in production of IL-6, IL-8, and TNFα. Supplementation with lutein suppressed LPS-stimulated production of these inflammatory mediators in both RPE and macrophages. These suppressive effects were dose dependent. Lutein supplementation to cultured RPE also suppressed the production of IL-6 and IL-8 in the absence of LPS stimulation. Furthermore, macrophages isolated from lutein-supplemented mice produced less IL-6 and TNFα upon LPS stimulation and the suppressive effects were also dose dependent. Supplementation with zeaxanthin suppressed the production of IL-8, but not IL-6. These data indicate that lutein and zeaxanthin have anti-inflammatory effects and that increased dietary lutein or zeaxanthin intake may reduce the risk for AMD via modulating ocular and systemic inflammation.