Abscisic acid inhibited reactive oxygen species-mediated endoplasmic reticulum stress by regulating the PPAR-γ signaling pathway in ARDS mice

Acute respiratory distress syndrome (ARDS) is a life-threatening form of a respiratory disorder, and there are few effective therapies. Abscisic acid (ABA) has been proven to be effective in influenza and asthma. Herein, we explored the protective effect of ABA on the resolution of ARDS and the underlying mechanism. Mice were challenged with lipopolysaccharide (LPS) to establish an ARDS model. We found that ABA reduced pulmonary injury, with concomitant suppression of endoplasmic reticulum (ER) stress and reduction of reactive oxygen species (ROS) production. Furthermore, after the elimination of ROS by the specific inhibitor N-acetyl-L-cysteine (NAC), ABA did not further inhibit airway inflammation or ER stress in ARDS mice. In addition, ABA inhibited ROS production through nuclear factor erythroid 2-related factor 2 (Nrf2) activation in parallel with elevated levels of peroxisome proliferator activated receptor gamma (PPAR-gamma). Furthermore, the addition of a PPAR-gamma antagonist abrogated the suppressive action of ABA on inflammation as well as on ER stress and oxidative stress, while NAC restored the protective effect of ABA in ARDS mice treated with a PPAR-gamma antagonist. Collectively, ABA protects against LPS-induced lung injury through PPAR-gamma signaling, and this effect may be associated with its inhibitory effect on ROS-mediated ER stress.

Automated summary

Studies have shown that abscisic acid (ABA) protects mice from lipopolysaccharide (LPS)-induced lung injury by activating nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator activated receptor gamma (PPARγ) signaling pathways. Its inhibitory effect on reactive oxygen species (ROS)-mediated endoplasmic reticulum stress may contribute to this protective mechanism.