Targeting Nrf2 and AP-1 stress signaling in acute lung injury and repair

International Conference and Exhibition on Lung Disorders & Therapeutics

July 13-15, 2015 Baltimore, Maryland, USA

Sekhar P Reddy

Posters-Accepted Abstracts: J Pulm Respir Med

Abstract :

Oxidative stress has been implicated in acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS) both of which are clinical disorders with significant morbidity and mortality. Cellular stress related to oxygen supplementation (or hyperoxia) which is used as a therapy to maintain adequate tissue oxygenation in pre-term babies has been linked to the development of bronchopulmonary disease (BPD), a chronic lung disease with significant morbidity and mortality. Dr Reddyâ??s lab research is focused primarily on understanding the exact mechanisms underlying defective lung tissue repair and persistent inflammation that are known to enhance susceptibility to bacterial/viral infection in ALI/ARDS patients leading to morbidity and often death in adults and neonates. We found that disruption of the Nrf2 transcription factor which is crucial for antioxidant gene expression impairs the resolution of oxidant (hyperoxia)-induced acute lung injury leading to defective lung tissue repair and persistent inflammation in both neonatal and adult mice. Importantly, our findings revealed that Nrf2 deficiency promotes susceptibility to bacterial infection after hyperoxic exposure ultimately leading to death of the host.We are using both genetic and pharmacologic approaches to elucidate the exact mechanisms by which Nrf2 and AP-1 signaling balance mediate the resolution of lung injury as a means of gaining insight into the development and perpetuation of ALI leading to infectious complications in neonates and adults. We are exploring how to pharmacologically amplify Nrf2- regulated signaling as a novel means to intervene and improve the outcomes of ALI and BPD using preclinical models and ex vivo samples.