Disruption of Nrf2 Enhances Upregulation of Nuclear Factor-κB Activity, Proinflammatory Cytokines, and Intercellular Adhesion Molecule-1 in the Brain after Traumatic Brain Injury

作者：Jin, Wei; Wang, Handong^*; Yan, Wei; Xu, Lizhi; Wang, Xiaoliang; Zhao, Xiaoning; Yang, Xiaohe; Chen, Gang; Ji, Yan

来源：Mediators of Inflammation, 2008, 2008: 725174.

DOI：10.1155/2008/725174

• TRANSCRIPTION FACTOR
• NRF2-DEFICIENT MICE
• INFLAMMATION
• SUSCEPTIBILITY
• PATHWAY
• EXPRESSION
• INDUCTION
• OXIDANTS
• GENES
• MODEL

Inflammatory response plays an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that plays a crucial role in cytoprotection against inflammation. The present study investigated the role of Nrf2 in the cerebral upregulation of NF-kappa B activity, proinflammatory cytokine, and ICAM-1 after TBI. Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact head injury. Electrophoretic mobility shift assays (EMSAs) were performed to analyze the activation of nuclear factor kappa B (NF-kappa B). Enzyme-linked immunosorbent assays were performed to quantify the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6). Immunohistochemistry staining experiments were performed to detect the expression of intercellular adhesion molecule-1 (ICAM-1). Nrf2 (-/-) mice were shown to have more NF-kappa B activation, inflammatory cytokines TNF-alpha, IL-1 beta and IL-6 production, and ICAM-1 expression in brain after TBI compared with their wild-type Nrf2 (+/+) counterparts. The results suggest that Nrf2 plays an important protective role in limiting the cerebral upregulation of NF-kappa B activity, proinflammatory cytokine, and ICAM-1 after TBI.

• 出版日期2008
• 单位南京大学; 浙江大学