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

Jin W, Wang H, Yan W, Xu L, Wang X, Zhao X, Yang X, Chen G, Ji Y - Mediators Inflamm. (2009)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.

ABSTRACT
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.

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Related in: MedlinePlus

NF-κB activity in the cortex of sham and injured Nrf2 (+/+)and Nrf2 (−/−) mice. (a) Nuclear proteins of brainsamples of Nrf2 (+/+) and Nrf2 (−/−) mice were assayed for NF-κB DNA bindingactivity by EMSA 24 hours after TBI. (b) Quantification of NF-κB DNA bindingactivity was performed by densitometric analysis. The figure indicates thatcerebral NF-κB activity was significantly increased after TBI and was greaterin Nrf2 (−/−) mice than in Nrf2 (+/+) mice. Datarepresents mean ± SEM (n = 5 per group). **P < .01 versus sham control of thesame genotype. ##P < .01 versus injured wild-typemice.
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fig2: NF-κB activity in the cortex of sham and injured Nrf2 (+/+)and Nrf2 (−/−) mice. (a) Nuclear proteins of brainsamples of Nrf2 (+/+) and Nrf2 (−/−) mice were assayed for NF-κB DNA bindingactivity by EMSA 24 hours after TBI. (b) Quantification of NF-κB DNA bindingactivity was performed by densitometric analysis. The figure indicates thatcerebral NF-κB activity was significantly increased after TBI and was greaterin Nrf2 (−/−) mice than in Nrf2 (+/+) mice. Datarepresents mean ± SEM (n = 5 per group). **P < .01 versus sham control of thesame genotype. ##P < .01 versus injured wild-typemice.

Mentions: NF-κB activation in the nuclearextracts was assessed by EMSA. As shown inFigure 2, low NF-κB banding activity(weak EMSA autoradiography) was observed in sham-operated mice of bothgenotypes. TBI induced activation of NF-κB in the cortexof both Nrf2 (+/+) and Nrf2 (−/−) mice. Nrf2 (−/−) mice showed an increasedsusceptibility to TBI-induced activation of NF-κB than their wild-type Nrf2 (+/+) counterparts.


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

Jin W, Wang H, Yan W, Xu L, Wang X, Zhao X, Yang X, Chen G, Ji Y - Mediators Inflamm. (2009)

NF-κB activity in the cortex of sham and injured Nrf2 (+/+)and Nrf2 (−/−) mice. (a) Nuclear proteins of brainsamples of Nrf2 (+/+) and Nrf2 (−/−) mice were assayed for NF-κB DNA bindingactivity by EMSA 24 hours after TBI. (b) Quantification of NF-κB DNA bindingactivity was performed by densitometric analysis. The figure indicates thatcerebral NF-κB activity was significantly increased after TBI and was greaterin Nrf2 (−/−) mice than in Nrf2 (+/+) mice. Datarepresents mean ± SEM (n = 5 per group). **P < .01 versus sham control of thesame genotype. ##P < .01 versus injured wild-typemice.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2630405&req=5

fig2: NF-κB activity in the cortex of sham and injured Nrf2 (+/+)and Nrf2 (−/−) mice. (a) Nuclear proteins of brainsamples of Nrf2 (+/+) and Nrf2 (−/−) mice were assayed for NF-κB DNA bindingactivity by EMSA 24 hours after TBI. (b) Quantification of NF-κB DNA bindingactivity was performed by densitometric analysis. The figure indicates thatcerebral NF-κB activity was significantly increased after TBI and was greaterin Nrf2 (−/−) mice than in Nrf2 (+/+) mice. Datarepresents mean ± SEM (n = 5 per group). **P < .01 versus sham control of thesame genotype. ##P < .01 versus injured wild-typemice.
Mentions: NF-κB activation in the nuclearextracts was assessed by EMSA. As shown inFigure 2, low NF-κB banding activity(weak EMSA autoradiography) was observed in sham-operated mice of bothgenotypes. TBI induced activation of NF-κB in the cortexof both Nrf2 (+/+) and Nrf2 (−/−) mice. Nrf2 (−/−) mice showed an increasedsusceptibility to TBI-induced activation of NF-κB than their wild-type Nrf2 (+/+) counterparts.

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus