Influence of Nrf2 genotype on pulmonary NF-kappaB activity and inflammatory response after traumatic brain injury.
Inflammatory response plays an important role in the pathogenesis of acute lung injury (ALI) 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 explored the influence of Nrf2 genotype on the production of cytokines and on activation of transcription factors in a murine TBI model. Wild-type Nrf2 (+/+) and Nrf2 (-/-) deficient mice were subjected to a moderately severe weight-drop impact-acceleration head injury. Lung wet/dry weight ratio, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and nuclear factor kapp-aB (NF-kappaB) were investigated at 24 hr after TBI. Nrf2 (-/-) mice were shown to have a greater increase in the lung wet/dry weight ratio compared to their wild-type Nrf2 (+/+) counterparts after TBI. This exacerbation of lung injury in Nrf2 (-/-) mice was associated with increased levels of TNF-alpha, IL-1beta, IL-6, ICAM-1, and their mediator, NF-kappaB. The results suggest that Nrf2 plays an important protective role in attenuating the pulmonary inflammatory response and NF-kappaB activation after TBI.
Jin
Wei
W
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Zhu
Lin
L
Guan
Qun
Q
Chen
Gang
G
Wang
Qing Feng
QF
Yin
Hong Xia
HX
Hang
Chun Hua
CH
Shi
Ji Xin
JX
Wang
Han Dong
HD
D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D005838:Genotype; D007249:Inflammation / Q000150:complications*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009929:Organ Size
D016207:Cytokines; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D018799:Intercellular Adhesion Molecule-1