Kim Jiyoung, Surh Young-Joon
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 599 Kwanak-ro, Kwanak-gu, Seoul, 151-742 Korea.
Toxicol Res. 2009 Dec;25(4):159-173. doi: 10.5487/TR.2009.25.4.159. Epub 2009 Dec 30.
Nuclear factor erythroid derived 2-related factor-2 (Nrf2) is a master transcription regulator of antioxidant and cytoprotective proteins that mediate cellular defense against oxidative and inflammatory stresses. Disruption of cellular stress response by Nrf2 deficiency causes enhanced susceptibility to infection and related inflammatory diseases as a consequence of exacerbated immuneediated hypersensitivity and autoimmunity. The cellular defense capacity potentiated by Nrf2 activation appears to balance the population of CD4 and CD8 of lymph node cells for proper innate immune responses. Nrf2 can negatively regulate the activation of pro-inflammatory signaling molecules such as p38 MAPK, NF-KB, and AP-1. Nrf2 subsequently functions to inhibit the production of pro-inflammatory mediators including cytokines, chemokines, cell adhesion molecules, matrix metalloprotein-ases, COX-2 and iNOS. Although not clearly elucidated, the antioxidative function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the expression of proinflammatory mediators.
核因子红细胞衍生2相关因子2（Nrf2）是抗氧化和细胞保护蛋白的主要转录调节因子，这些蛋白介导细胞对氧化和炎症应激的防御。由于免疫介导的超敏反应和自身免疫加剧，Nrf2缺乏导致细胞应激反应破坏，从而增加对感染和相关炎症性疾病的易感性。Nrf2激活增强的细胞防御能力似乎平衡了淋巴结细胞中CD4和CD8的数量，以实现适当的先天免疫反应。Nrf2可以负向调节促炎信号分子如p38丝裂原活化蛋白激酶（p38 MAPK）、核因子κB（NF-κB）和活化蛋白1（AP-1）的激活。Nrf2随后发挥作用，抑制包括细胞因子、趋化因子、细胞粘附分子、基质金属蛋白酶、环氧化酶-2（COX-2）和诱导型一氧化氮合酶（iNOS）在内的促炎介质的产生。尽管尚未明确阐明，但Nrf2靶向基因的抗氧化功能可能协同调节先天免疫反应，并抑制促炎介质的表达。
