Disruption of Nrf2 Enhances Upregulation of Nuclear Factor-κB 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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Main Authors: Wei Jin, Handong Wang, Wei Yan, Lizhi Xu, Xiaoliang Wang, Xiaoning Zhao, Xiaohe Yang, Gang Chen, Yan Ji
Format: Article
Language:English
Published: Wiley 2008-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2008/725174
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author Wei Jin
Handong Wang
Wei Yan
Lizhi Xu
Xiaoliang Wang
Xiaoning Zhao
Xiaohe Yang
Gang Chen
Yan Ji
author_facet Wei Jin
Handong Wang
Wei Yan
Lizhi Xu
Xiaoliang Wang
Xiaoning Zhao
Xiaohe Yang
Gang Chen
Yan Ji
author_sort Wei Jin
collection DOAJ
description 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-κB 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-κB). Enzyme-linked immunosorbent assays were performed to quantify the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), 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-κB activation, inflammatory cytokines TNF-α, IL-1β 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-κB activity, proinflammatory cytokine, and ICAM-1 after TBI.
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spelling doaj-art-265229dcd54542329fce140bdaf79bed2025-08-20T02:04:23ZengWileyMediators of Inflammation0962-93511466-18612008-01-01200810.1155/2008/725174725174Disruption of Nrf2 Enhances Upregulation of Nuclear Factor-κB Activity, Proinflammatory Cytokines, and Intercellular Adhesion Molecule-1 in the Brain after Traumatic Brain InjuryWei Jin0Handong Wang1Wei Yan2Lizhi Xu3Xiaoliang Wang4Xiaoning Zhao5Xiaohe Yang6Gang Chen7Yan Ji8Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, ChinaDepartment of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, ChinaDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, ChinaDepartment of Medical Genetics, School of Medicine, Nanjing University, Nanjing 210093, Jiangsu Province, ChinaDepartment of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, ChinaDepartment of Medical Genetics, School of Medicine, Nanjing University, Nanjing 210093, Jiangsu Province, ChinaDepartment of Medical Genetics, School of Medicine, Nanjing University, Nanjing 210093, Jiangsu Province, ChinaDepartment of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, ChinaDepartment of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital, School of Medicine, Nanjing University, Nanjing 210008, Jiangsu Province, ChinaInflammatory 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-κB 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-κB). Enzyme-linked immunosorbent assays were performed to quantify the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), 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-κB activation, inflammatory cytokines TNF-α, IL-1β 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-κB activity, proinflammatory cytokine, and ICAM-1 after TBI.http://dx.doi.org/10.1155/2008/725174
spellingShingle Wei Jin
Handong Wang
Wei Yan
Lizhi Xu
Xiaoliang Wang
Xiaoning Zhao
Xiaohe Yang
Gang Chen
Yan Ji
Disruption of Nrf2 Enhances Upregulation of Nuclear Factor-κB Activity, Proinflammatory Cytokines, and Intercellular Adhesion Molecule-1 in the Brain after Traumatic Brain Injury
Mediators of Inflammation
title Disruption of Nrf2 Enhances Upregulation of Nuclear Factor-κB Activity, Proinflammatory Cytokines, and Intercellular Adhesion Molecule-1 in the Brain after Traumatic Brain Injury
title_full Disruption of Nrf2 Enhances Upregulation of Nuclear Factor-κB Activity, Proinflammatory Cytokines, and Intercellular Adhesion Molecule-1 in the Brain after Traumatic Brain Injury
title_fullStr Disruption of Nrf2 Enhances Upregulation of Nuclear Factor-κB Activity, Proinflammatory Cytokines, and Intercellular Adhesion Molecule-1 in the Brain after Traumatic Brain Injury
title_full_unstemmed Disruption of Nrf2 Enhances Upregulation of Nuclear Factor-κB Activity, Proinflammatory Cytokines, and Intercellular Adhesion Molecule-1 in the Brain after Traumatic Brain Injury
title_short Disruption of Nrf2 Enhances Upregulation of Nuclear Factor-κB Activity, Proinflammatory Cytokines, and Intercellular Adhesion Molecule-1 in the Brain after Traumatic Brain Injury
title_sort disruption of nrf2 enhances upregulation of nuclear factor κb activity proinflammatory cytokines and intercellular adhesion molecule 1 in the brain after traumatic brain injury
url http://dx.doi.org/10.1155/2008/725174
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