Nrf2 protects against acute lung injury and inflammation by modulating TLR4 and Akt signaling.

Nrf2 protects against acute lung injury and inflammation by modulating TLR4 and Akt signaling.
Free Radic Biol Med. 2018 Apr 17;:
Authors: Yan J, Li J, Zhang L, Sun Y, Jiang J, Huang Y, Xu H, Jiang H, Hu R
Abstract
Lung injury, which is associated with systemic inflammatory responses, is a common problem with significant morbidity and mortality. Here, we examined the involvement of toll-like receptor 4 (TLR4) and nuclear factor erythroid 2-related factor 2 (Nrf2) on intestinal ischemia-reperfusion (I/R)-induced lung injury in vivo and in vitro. Analysis of lung tissues in Nrf2-knockout mice by western blotting, immunohistochemistry, and TUNEL assay, and analysis of bronchoalveolar lavage fluid showed that Nrf2 deficiency upregulated TLR4, enhanced I/R-induced lung injury, apoptosis, inflammation, and autophagy, and increased the I/R-induced inactivation of Akt. In mouse lung epithelial cells subjected to oxygen and glucose deprivation/reperfusion (OGD/Rep), Nrf2 silencing increased the OGD/Rep-induced upregulation of TLR4 and MyD88 and downregulation of HO-1, and exacerbated OGD/Rep-induced apoptosis, autophagy, and the downregulation of phospho-Akt. TLR4 silencing and Akt inhibition experiments indicated that OGD/Rep-induced cell death by suppressing Akt signaling, and Nrf2 protected lung cells by modulating TLR4 and Akt signaling. These results indicated that the Nrf2/TLR4/Akt axis plays a role in inflammation-associated lung damag...

Source: Free Radical Biology and Medicine - April 17, 2018 Category: Biology Authors: Yan J, Li J, Zhang L, Sun Y, Jiang J, Huang Y, Xu H, Jiang H, Hu R Tags: Free Radic Biol Med Source Type: research