Nrf2 is a critical modulator of the innate immune response in a model of uveitis.
Nrf2 is a critical modulator of the innate immune response in a model of uveitis.
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DOI：
10.1016/j.freeradbiomed.2009.04.033
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发表时间：
2009-08-01
影响因子：
7.4
通讯作者：
Handa, James T.
中科院分区：
文献类型：
--
作者：
Nagai, Norihiro;Thimmulappa, Rajesh K.;Cano, Marisol;Fujihara, Masashi;Izumi-Nagai, Kanako;Kong, Xiaoni;Sporn, Michael B.;Kensler, Thomas W.;Biswal, Shyam;Handa, James T.
关键词：
葡萄膜炎是一种炎症性疾病，可导致失明。因此，重要的是要了解的病理生理学上的发展靶向治疗。在此，我们测试了氧化剂响应性转录因子Nrf 2是否参与调节LPS葡萄膜炎模型中的先天免疫应答和氧化损伤。通过二氢乙锭染色，腹腔注射LPS增加了Nrf 2 +/+和Nrf 2 −/−小鼠视网膜和虹膜睫状体中的活性氧。LPS注射后，Nrf 2-/-小鼠视网膜和虹膜睫状体中ICAM-1、IL-6、TNF-α、考克斯-2、iNOS和MCP-1 mRNA的增加幅度大于Nrf 2 +/+小鼠。NQO-1和GCLM是两种Nrf 2响应性抗氧化酶，注射LPS后Nrf 2 +/+视网膜中的表达减少，但Nrf 2-/-小鼠中的表达没有变化。与对照注射相比，LPS处理后Nrf 2 +/+和Nrf 2 −/−小鼠中粘附于视网膜血管内皮的FITC-con A标记的白细胞数量增加，Nrf 2 −/−小鼠中粘附的白细胞多于Nrf 2 +/+小鼠。用Nrf 2激活剂1-（2-氰基-3-，12-二氧代齐墩果烷-1，9（11）-二烯-28-酰基）咪唑预处理，增加了视网膜中抗氧化基因的表达，减少了炎症介质的表达，并减少了LPS处理后Nrf 2 +/+小鼠视网膜血管系统的白细胞粘附，但对Nrf 2 −/−小鼠没有影响。针对Nrf 2通路的治疗可能是葡萄膜炎的新疗法。
Uveitis is an inflammatory condition that can lead to blindness. It is therefore, important to understand the pathophysiology on which to develop targeted therapy. Herein, we tested whether the oxidant-responsive transcription factor Nrf2 is involved in regulating the innate immune response and oxidative damage in the LPS uveitis model. With Dihydroethidium staining, intraperitoneally injected LPS increased reactive oxygen species in the retina and iris-ciliary body of Nrf2+/+ and Nrf2−/− mice. After LPS injection, ICAM-1, IL-6, TNF-α, COX-2, iNOS, and MCP-1 mRNA were increased more in the retina and iris-ciliary body of Nrf2−/− than Nrf2+/+ mice. NQO-1 and GCLM, two Nrf2 responsive anti-oxidant enzymes, had reduced expression in Nrf2+/+ retinas after LPS injection, but no change in expression in Nrf2−/− mice. The number of FITC-con A labeled leukocytes adherent to the retinal vascular endothelium increased after LPS treatment in both Nrf2+/+ and Nrf2−/− mice compared to control injections, with the more adherent leukocytes in Nrf2−/− than Nrf2+/+ mice. Pretreatment with the Nrf2 activator 1-(2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl)imidazole, increased antioxidant gene expression in the retina, reduced inflammatory mediator expression, and reduced leukocyte adherence to retinal vasculature after LPS treatment in Nrf2+/+ mice, but had no effect on Nrf2−/− mice. Treatment targeting the Nrf2 pathway may be new therapy for uveitis.
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影响因子：
4.4
作者：
Soares, MP;Seldon, MP;Bach, FH
通讯作者：
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作者：
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