Studying The Mechanisms of Delayed Lung Injury Post-Arsenical Exposures

Title: Studying The Mechanisms of Delayed Lung Injury Post-Arsenical Exposures Abstract In this study, we aim to investigate the mechanisms of delayed lung injury after a single exposure to trivalent arsenic chemical agents: Lewisite, Phenyl arsenic oxide, and arsenic trioxide. Our research using murine models has shown that skin exposure to Lewisite and Phenyl arsenic oxide, as well as single inhalation exposure to arsenic trioxide, leads to persistent systemic inflammation and fibrotic airway-centered chronic bronchitis. Additionally, in our model, we observed that single exposure to arsenic trioxide exposure led to hemolytic anemia-like lung disorder. We hypothesize that trivalent arsenic injury triggers the release of self- double-stranded DNA in the form of NETs, which activate IRF7 in airway epithelial cells. This activation leads to the transcription of type I interferons, initiating a feed-forward loop of IL-33 signaling that contributes to airway fibrogenesis in Lewisite/Phenyl arsenic oxide-exposed mice and persistent IFN-type I inflammation in arsenic trioxide-exposed mice. We are investigating how a single dose of trivalent arsenic induces mechanisms of NETs-IRF7-IL33 signaling, leading to persistent inflammation and implicating chronic lung disorders.