title: Genetic ablation of Nrf2 enhances susceptibility to acute lung injury after traumatic brain injury in mice.
abstract: Previous studies have shown that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a unique role in many physiological stress processes. The present study investigated the role of Nrf2 in the regulation of traumatic brain injury (TBI)-induced acute lung injury (ALI). Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact head injury. Pulmonary capillary permeability (PCP), wet/dry weight ratio, apoptosis, inflammatory cytokines and antioxidant/detoxifying enzymes were measured at 24 h after TBI. Mice lacking Nrf2 were found to be more susceptible to TBI-induced ALI, as characterized by the higher increase in PCP, wet/dry weight ratio and alveolar cells apoptosis after TBI. This exacerbation of lung injury in Nrf2-deficient mice was associated with increased pulmonary mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6); and with decreased pulmonary mRNA expression and enzymatic activities of antioxidant and detoxifying enzymes including NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase alpha1 (GST-alpha1)--as compared with their wild-type Nrf2 (+/+) counterparts after TBI. The results of the present study suggest that Nrf2 reduces TBI-induced acute lung injury, possibly by decreasing pulmonary inflammation and inducing antioxidant and detoxifying enzymes.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Ji
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yin
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D001930:Brain Injuries / Q000150:complications* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002196:Capillaries / Q000503:physiopathology; D002199:Capillary Permeability / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004198:Disease Susceptibility; D017353:Gene Deletion; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone); D009252:NADPH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D009929:Organ Size; D011654:Pulmonary Edema / Q000150:complications / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D012333:RNA, Messenger; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D009252:NADPH Dehydrogenase