Influence of Nrf2 genotype on pulmonary NF-κB 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, Minor necrosis factor-CA (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and nuclear factor kappaB (NF-kappa B) 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-1 beta, IL-6, ICAM-1, and their mediator, NF-kappa B. The results suggest that Nrf2 plays ail important protective role in attenuating the Pulmonary inflammatory response and NF-kappa B activation after TBI.