...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A β-oxidation-resistant lipoxin A_4 analog treats hapten-induced colitis by attenuating inflammation and immune dysfunction
【24h】

A β-oxidation-resistant lipoxin A_4 analog treats hapten-induced colitis by attenuating inflammation and immune dysfunction

机译：抗β氧化的脂蛋白A_4类似物通过减轻炎症和免疫功能障碍来治疗半抗原诱发的结肠炎

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Lipoxins and aspirin-triggered 15-epi-lipoxins (ATL) are counter-regulatory eicosanoids with potent antiinflammatory actions. Oral efficacy and mechanism of action of ZK-192, a β-oxidation-resistant 3-oxa-ATL analog, were examined in trinitrobenzenesulphonate (TNBS)-induced colitis. When dosed orally once daily, 300 and 1,000 μg/kg ZK-192 markedly attenuated TNBS colitis in rodents both in preventive and therapeutic regimens. ZK-192 attenuated weight loss, macroscopic and histologic colon injury, mucosal neutrophil infiltration, and colon wall thickening. ZK-192 was as effective as 3-10 mg/kg oral prednisolone. ZK-192 decreased mucosal mRNA levels for several inflammatory mediators: inducible nitric oxide synthase, cyclooxygenase 2, and macrophage inflammatory protein 2. ZK-192 also decreased mucosal mRNA and protein levels of T helper 1 effector cytokines: tumor necrosis factor α, IL-2, and IFN-γ. Systemic levels of these cytokines were also dramatically attenuated. CD3/CD28-mediated costimulation of T helper 1 effector cytokine release in lamina propria mononuclear cells was markedly inhibited by ZK-192 ex vivo and in vitro. ZK-192 also prevented colitis in lymphocyte-deficient severe combined immu-nodeficient mice, with ≈75% inhibition of mucosal tumor necrosis factor α and IL-2 levels. The results are further evidence that innate immune cells function as triggers for hapten-induced colitis. The combined antiinflammatory and immunomodulatory effects of ZK-192 in TNBS colitis suggest that ATL analogs may be an attractive oral treatment approach for inflammatory bowel diseases.
机译：脂蛋白和阿司匹林触发的15表脂类脂蛋白（ATL）是具有有效抗炎作用的反调节类二十烷酸。在三硝基苯磺酸盐（TNBS）诱发的结肠炎中检查了抗β-氧化的3-oxa-ATL类似物ZK-192的口服疗效和作用机理。每天口服一次，在预防和治疗方案中，分别以300和1,000μg/ kg的ZK-192显着减轻啮齿动物的TNBS结肠炎。 ZK-192可减轻体重减轻，宏观和组织学结肠损伤，粘膜中性粒细胞浸润以及结肠壁增厚。 ZK-192与口服泼尼松龙3-10 mg / kg一样有效。 ZK-192降低了几种炎性介质的黏膜mRNA水平：诱导型一氧化氮合酶，环氧合酶2和巨噬细胞炎性蛋白2。ZK-192还降低了T辅助1效应细胞因子的黏膜mRNA和蛋白水平：肿瘤坏死因子α，IL- 2，IFN-γ。这些细胞因子的全身水平也显着减弱。 ZK-192体外和体外显着抑制固有层固有核中T辅助细胞1辅助因子的CD3 / CD28介导的共刺激。 ZK-192还可以预防淋巴细胞不足的严重合并免疫缺陷小鼠的结肠炎，对粘膜肿瘤坏死因子α和IL-2水平的抑制作用约为75％。该结果进一步证明了先天免疫细胞是半抗原诱发的结肠炎的触发因子。 ZK-192在TNBS结肠炎中的综合抗炎和免疫调节作用表明ATL类似物可能是炎性肠病的一种有吸引力的口服治疗方法。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号