Increased intestinal inflammatory response and gut barrier dysfunction in Nrf2-deficient mice after traumatic brain injury.
OBJECTIVE
To explore the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in traumatic brain injury (TBI)-induced intestinal inflammatory response and gut barrier dysfunction in the mice.


METHODS
Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact-acceleration head injury. We measured nuclear factor kappa B (NF-kappaB) by electrophoretic mobility shift assay (EMSA); tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA); intercellular adhesion molecule-1 (ICAM-1) by immunohistochemistry; intestinal permeability by lactulose/mannitol (L/M) test; plasma endotoxin by chromogenic limulus amebocyte lysate test.


RESULTS
Intestinal levels of NF-kappaB, pro-inflammatory cytokines and ICAM-1 in Nrf2 (-/-)-deficient mice were significantly higher compared with Nrf2 (+/+) mice at 24h after TBI. Furthermore, higher intestinal permeability and plasma level of endotoxin were observed in the Nrf2 (-/-) mice compared with Nrf2 (+/+) mice.


CONCLUSIONS
Nrf2 plays an important protective role in limiting intestinal inflammatory response and gut barrier dysfunction after TBI.
Jin
Wei
W
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, PR China.
Wang
Handong
H
Ji
Yan
Y
Hu
Qingang
Q
Yan
Wei
W
Chen
Gang
G
Yin
Hongxia
H
D000818:Animals; D001930:Brain Injuries / Q000150:complications* / Q000503:physiopathology*; D004731:Endotoxins / Q000097:blood; D007249:Inflammation / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000503:physiopathology; D007422:Intestines / Q000276:immunology*; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000172:deficiency*; D016328:NF-kappa B / Q000378:metabolism; D010539:Permeability; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D053583:Interleukin-1beta; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1