Disruption of Nrf2 enhances upregulation of nuclear factor-kappaB activity, proinflammatory cytokines, and intercellular adhesion molecule-1 in the brain after traumatic brain injury

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 investi...

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Bibliographic Details
Published in:Mediators of inflammation 2008, Vol.2008, p.725174-725174
Main Authors: Jin, Wei, Wang, Handong, Yan, Wei, Xu, Lizhi, Wang, Xiaoliang, Zhao, Xiaoning, Yang, Xiaohe, Chen, Gang, Ji, Yan
Format: Article
Language:English
Subjects:
Animals
Brain - metabolism
Brain Injuries - metabolism
Cytokines - analysis
Cytokines - biosynthesis
Electrophoretic Mobility Shift Assay
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Intercellular Adhesion Molecule-1 - analysis
Mice
Mice, Inbred ICR
NF-E2-Related Factor 2 - physiology
NF-kappa B - metabolism
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Summary: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-kappaB 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-kappaB). Enzyme-linked immunosorbent assays were performed to quantify the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), 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-kappaB activation, inflammatory cytokines TNF-alpha, IL-1beta 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-kappaB activity, proinflammatory cytokine, and ICAM-1 after TBI.
ISSN:1466-1861
DOI:10.1155/2008/725174