摘要
Nrf2(Nuclear factor-erythroid 2-rdated factor-2)在细胞受到氧化物或亲电子攻击时会及时诱导抗氧化,Ⅱ相解毒酶和相关应激反应蛋白的产生,起到重要的细胞保护作用,是一个关键又重要的转录因子。近来研究表明Nrf2/ARE信号通路也参与抑制炎症相关疾病,如自身免疫疾病、风湿类关节炎、哮喘、肺气肿、胃炎、结肠炎和动脉粥样硬化等。扰乱Nrf2信号不仅会增加机体对氧化物,电子攻击的敏感性,还会加重炎症组织的损伤。在炎症介导的组织损伤早期,Nrf2/ARE的激活可能会抑制促炎介质的产生及表达,包括细胞因子,炎症趋化因子,细胞粘附因子,基质金属蛋白酶,环氧化酶2(COX-2),诱导性一氧化氮合酶(iNOS)。与此同时,Nrf2介导的具有细胞保护能力的下游基因会参与调节先天免疫应答,同时抑制促炎基因的表达。该综述强调Nrf2在炎症相关疾病中的保护作用,侧重此转录因子对炎症信号的调节。
Nuclear factor-erythroid 2-related factor-2 （Nrf2） is a key transcription factor that plays a central role in cellular defense against oxidative and electrophilic insults by timely induction of antioxidative and phase-2 detoxifying enzymes and related stress- response proteins. The recent studies have demonstrated that Nrf2-ARE signaling is also involved in attenuating inflammation-associ- ated pathogenesis, such as autoimmune diseases, rheumatoid arthritis, asthma, emphysema, gastritis, colitis and atherosclerosis. Thus, disruption or loss of Nrf2 signaling may cause the enhanced susceptibility not only to oxidative and electrophilic stresses but also to inflammatory tissue injuries. During the early-phase of inflammation-mediated tissue damage, the activation of Nrf2-ARE might inhibit the production or expression of pro-inflammatory mediators including cytokines, ehemokines, cell adhesion molecules, matrix metallo- proteinases, cyclooxygenase-2 and inducible nitric oxide synthase. It is likely that the cytoprotective function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the induction of pro-inflammatory genes. This review high- lights the protective role of Nrf2 in inflammation-mediated disorders with special focus on the inflammatory signaling modulated by this redox-regulated transcription factor.
出处
《药物生物技术》
CAS
2013年第4期353-356,共4页
Pharmaceutical Biotechnology
