Double edged roles of endogenous PRDX6 in ventilator-induced lung injury via modulating oxidative stress and macrophages activation

PRDX6 is highly expressed in lung tissues and shows an important biological significance. However, its specific roles in ventilator-induced lung injury (VILI) have not been clearly explored. The present study investigated the roles of endogenous PRDX6 in VILI, focusing on its overall and the iPLA2 function on lung injury, oxidative stress (OS), macrophages activation and polarization. Broncho-alveolar lavage fluid (BALF) from patients with mechanical ventilation was acquired. Both wild-type (WT) Sprague-Dawley rats and PRDX6 gene-knock out (PRDX6 ^-/- ) rats were used to set up VILI model. Biological and histopathological analyses were performed. Our results showed that OS and PRDX6 expression were up-regulated after mechanical ventilation. PRDX6 deficiency led to lung inflammation and VILI aggravation, and the OS was further elevated and the activation and M1 polarization of lung macrophages were obviously increased in PRDX6 ^-/- rats. The iPLA2 inhibitor MJ33 alleviated VILI in rats and reversed the increased OS and M1 macrophages activation and polarization. The present study showed the double-edged roles of endogenous PRDX6 in VILI, including its overall protective role and the role of promoting VILI via iPLA2 by producing the excessive OS and subsequent increase of M1 macrophages polarization.