Disruption of Nrf2 Enhances Upregulation of Nuclear Factor‐ κ B Activity, Proinflammatory Cytokines, and Intercellular Adhesion Molecule‐1 in the Brain after Traumatic Brain Injury
Open accessAbstract
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‐ κ 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‐ κ B). Enzyme‐linked immunosorbent assays were performed to quantify the production of tumor necrosis factor‐ α (TNF‐ α ), interleukin‐1 β (IL‐1 β ), 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‐ κ B activation, inflammatory cytokines TNF‐ α , IL‐1 β 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‐ κ B activity, proinflammatory cytokine, and ICAM‐1 after TBI.
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NF-κB increases oxidative stress by inhibiting NFE2L2 transcription through repression of CBP binding and by inducing ARE hypoacetylation.
“Inversely, NF-κB increases oxidative stress by inhibiting NFE2L2 transcription through repression of its creb binding protein (CBP) binding and by inducing ARE hypoacetylation 97 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [97]
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Cites
Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., et al. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6943 · Cited by 3,999 · see citing works
Baeuerle, P. A., & Baltimore, D. (1996) · Cell · doi:10.1016/s0092-8674(00)81318-5 · Cited by 3,002 · see citing works
Leukocyte-endothelial adhesion molecules
Carlos, T., & Harlan, J. (1994) · Blood · doi:10.1182/blood.v84.7.2068.bloodjournal8472068 · Cited by 2,500 · see citing works
Leukocyte-endothelial adhesion molecules
Carlos, T., & Harlan, J. (1994) · Blood · doi:10.1182/blood.v84.7.2068.2068 · Cited by 1,957 · see citing works
Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis
Thimmulappa, R. K. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25790 · Cited by 1,028 · see citing works
Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke–induced emphysema in mice
Rangasamy, T., Cho, C. Y., Thimmulappa, R. K., Zhen, L., Srisuma, S., Kensler, T. W., Yamamoto, M. P., Petrache, I., Tuder, R. M., & Biswal, S. S. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21146 · Cited by 993 · see citing works
Neurath, M. F., Pettersson, S., Büschenfelde, K. M. Z., & Strober, W. (1996) · Nature Medicine · doi:10.1038/nm0996-998 · Cited by 822 · see citing works
Cytokine Serum Level During Severe Sepsis in Human IL-6 as a Marker of Severity
DAMA, P., Ledoux, D., Nys, M., Vrindts, Y., Groote, D. D., Franchimont, P., & Lamy, M. (1992) · Annals of Surgery · doi:10.1097/00000658-199204000-00009 · Cited by 808 · see citing works
An Important Role of Nrf2-ARE Pathway in the Cellular Defense Mechanism
Lee, J., & Johnson, J. A. (2004) · BMB Reports · doi:10.5483/bmbrep.2004.37.2.139 · Cited by 746 · see citing works
Chen, F., Castranova, V., Shi, X., & Demers, L. M. (1999) · Clinical Chemistry · doi:10.1093/clinchem/45.1.7 · Cited by 719 · see citing works
Cytokines in inflammatory brain lesions: helpful and harmful
Merrill, J. E., & Benveniste, E. N. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10047-3 · Cited by 715 · see citing works
Disruption of <i>Nrf2</i> enhances susceptibility to severe airway inflammation and asthma in mice
Rangasamy, T., Guo, J., Mitzner, W. A., Roman, J., Singh, A., Fryer, A. D., Yamamoto, M., Kensler, T. W., Tuder, R. M., Georas, S. N., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050538 · Cited by 580 · see citing works
Cytokine appearance in human endotoxemia and primate bacteremia.
HESSE, D. G., Tracey, K. J., Fong, Y., Manogue, K. R., Palladino, M. A., Cerami, A., Shires, G. T., & Lowry, S. F. (1988) · PubMed · Cited by 532 · see citing works
Nrf2-Deficient Mice Have an Increased Susceptibility to Dextran Sulfate Sodium–Induced Colitis
Khor, T. O., Huang, M., Kwon, K. H., Chan, J. Y., Reddy, B. S., & Kong, A. T. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-3562 · Cited by 530 · see citing works
Antioxidants and oxidants regulated signal transduction pathways
Owuor, E. D., & Kong, A. T. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)01137-1 · Cited by 439 · see citing works
Braun, S., Hanselmann, C., Gassmann, M. G., auf dem Keller, U., Born-Berclaz, C., Chan, K., Kan, Y. W., & Werner, S. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.15.5492-5505.2002 · Cited by 410 · see citing works
Chen, X., & KUNSCH, C. A. (2004) · Current Pharmaceutical Design · doi:10.2174/1381612043452901 · Cited by 387 · see citing works
Primer: inflammasomes and interleukin 1β in inflammatory disorders
Church, L. D., Cook, G. P., & McDermott, M. (2008) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0681 · Cited by 312 · see citing works
Intracerebral Inflammation after Human Brain Contusion
Holmin, S., Söderlund, J., Biberfeld, P., & Mathiesen, T. I. (1998) · Neurosurgery · doi:10.1097/00006123-199802000-00047 · Cited by 268 · see citing works
Inflammation in Traumatic Brain Injury: Role of Cytokines and Chemokines
Ghirnikar, R. S., Lee, Y. L., & Eng, L. F. (1998) · Neurochemical Research · doi:10.1023/a:1022453332560 · Cited by 261 · see citing works
Role of Oxidants in Lung Injury During Sepsis
Guo, R., & Ward, P. A. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1785 · Cited by 246 · see citing works
High-dose glucocorticoid treatment improves neurological recovery in head-injured mice
Hall, E. D. (1985) · Journal of neurosurgery · doi:10.3171/jns.1985.62.6.0882 · Cited by 226 · see citing works
Osburn, W. O., Wakabayashi, N., Misra, V., Nilles, T. L., Biswal, S. S., Trush, M. A., & Kensler, T. W. (2006) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2006.08.005 · Cited by 225 · see citing works
Osburn, W. O., Karim, B. O., Dolan, P. M., Liu, G., Yamamoto, M. P., Huso, D. L., & Kensler, T. W. (2007) · International Journal of Cancer · doi:10.1002/ijc.22943 · Cited by 197 · see citing works
Hang, C., Shi, J., Tian, J., Li, J., Wu, W., & Yin, H.-X. (2004) · Brain Research · doi:10.1016/j.brainres.2004.07.090 · Cited by 121 · see citing works
Chen, G., Shi, J. X., Hang, C. H., et al. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.08.022 · Cited by 119 · see citing works
Self-citationKupina, N. C., Nath, R., Bernath, E., Inoue, J., Azuma, M., Yuen, P., Wang, K., & Hall, E. D. (2001) · Journal of Neurotrauma · doi:10.1089/089771501317095269 · Cited by 111 · see citing works
Activation of Nrf2–ARE pathway in brain after traumatic brain injury
Yan, W. X., Wang, H., Hu, Z.-G., Wang, Q.-F., & Yin, H.-X. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2007.11.060 · Cited by 97 · see citing works
Self-citationShohami, E., Gati, I., Beit‐Yannai, E., Trembovler, V., & Kohen, R. (1999) · Journal of Neurotrauma · doi:10.1089/neu.1999.16.365 · Cited by 85 · see citing works
Cortical expression of nuclear factor κB after human brain contusion
Hang, C., Chen, G., Shi, J., et al. (2006) · Brain Research · doi:10.1016/j.brainres.2006.06.045 · Cited by 76 · see citing works
Self-citationThe Inflammation in the Gut After Experimental Subarachnoid Hemorrhage
Zhou, M., Zhu, L., Wang, J., Hang, C., & Shi, J. (2006) · Journal of Surgical Research · doi:10.1016/j.jss.2006.06.023 · Cited by 31 · see citing works
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Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis
Hardingham, G. E., & Do, K. Q. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.19 · Cited by 304 · see citing works
Filipović, D., Todorović, N., Bernardi, R. E., & Gass, P. (2017) · Brain Structure and Function · doi:10.1007/s00429-016-1218-9 · Cited by 138 · see citing works
- Authors
- Jin, W., Wang, H., Yan, W., Xu, L., Wang, X., Zhao, X., Yang, X., Chen, G., & Ji, Y.
- Affiliations
- Nanjing General Hospital of Nanjing Military Command (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- Nanjing University (CN)
- Corresponding author
- Wang, Handong
- Venue
- Mediators of Inflammation
- Publisher
- Wiley
- Published
- 2008-01
- Volume
- 2008
- Issue
- 1
- Pages
- 725174-725174
- ISSN
- 0962-9351 (ISSN-L)
- 1466-1861
- PMC
- PMC2630405
- OpenAlex
- W1997007516
- Cited by
- 172
- References
- 31
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 11 · 2023: 4 · 2022: 9 · 2021: 3 · 2020: 7 · 2019: 8 · 2018: 10 · 2017: 15 · 2016: 10 · 2015: 14 · 2014: 13 · 2013: 18 · 2012: 12
- FWCI
- 6.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Mediators of Inflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Jinling Hospital of China
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- Nrf2, traumatic brain injury, NF-κB activation, inflammatory cytokines, TNF-α, IL-1β, interleukin-6, ICAM-1, neuroinflammation, secondary brain injury, Nrf2 knockout mice
- MeSH terms
- Animals, Brain, Brain Injuries, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Mice, Inbred ICR, Cytokines, NF-kappa B, Intercellular Adhesion Molecule-1, Electrophoretic Mobility Shift Assay, NF-E2-Related Factor 2, Mice
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