11 - Lung epithelial specific heme oxygenase-1 deletion does not worsen hyperoxic lung injury in adult mice

Abstract

Thioredoxin reductase-1 (TXNRD1) inhibition activates nuclear factor (erythroid-derived 2)-like 2(Nrf2) responses and prevents acute lung injury (ALI). Heme oxygenase-1 (HO-1) induction following TXNRD1 inhibition is Nrf2-dependent in airway epithelial (club) cells in vitro. To evaluate the contribution of HO-1 toward the protective effects of TXNRD1 inhibitors in vivo, a club cell specific HO-1 knockout (KO) mouse is needed. The present studies characterized the effects of hyperoxia on club cell specific HO-1 KO mice that were generated by crossing HO-1 floxed mice with transgenic mice expressing cre recombinase under control of a club cell specific promoter. Twelve-week old wildtype (WT) and KO mice were continuously exposed to >95% hyperoxia (HYP) or room air (RA) for 72h. Following exposure, mice were sacrificed and weighed. The left lung was inflation fixed and the right lung was collected and weighed. Injury was quantitatively assessed by calculating right lung/body weight ratios (g/kg) and qualitatively assessed in HE features that appeared to be more prominent in KO/HYP mice. In conclusion, lung epithelial cell HO-1 deletion does not alter hyperoxic lung injury in adult mice. Future studies will utilize this unique transgenic model to evaluate the contribution HO-1 toward the protective effects of TXNRD1 inhibitors in vivo.