Original ContributionOmeprazole attenuates hyperoxic injury in H441 cells via the aryl hydrocarbon receptor
Highlights
► Omeprazole treatment attenuates hyperoxia-induced ROS generation and inflammation. ► Omeprazole protects pulmonary cells against oxygen cytotoxicity. ► Omeprazole induces human CYP1A1 in H441 cells via the aryl hydrocarbon receptor. ► Aryl hydrocarbon receptor knockdown abrogates the beneficial effects of omeprazole.
Section snippets
Cell culture and treatment
H441 cells, a human lung adenocarcinoma epithelial cell line, obtained from American Type Culture Collection (Manassas, VA, USA), were grown in RPMI 1640 medium (Invitrogen, Carlsbad, CA, USA) containing 10% fetal bovine serum, 50 U/ml penicillin, and 50 U/ml streptomycin, in 95% air and 5% CO2 at 37 °C. Cells were treated with either dimethyl sulfoxide (DMSO) (Sigma–Aldrich, St. Louis, MO, USA) or 2 (OM2) or 5 μM (OM5) omeprazole (Sigma–Aldrich) for 4 h, followed by exposure to room air or
Results
In this study, we investigated the effects of omeprazole on the functional activation of AhR and its impact on hyperoxic injury in the human lung-derived H441 cells in vitro.
Discussion
This study demonstrates that the proton pump inhibitor omeprazole attenuates hyperoxic injury in vitro via the AhR, which is associated with decreased ROS generation and MCP-1 production. In human lung-derived H441 cells in vitro, omeprazole-mediated protection against hyperoxic injury correlated with the functional activation of the AhR by omeprazole compared to controls, whereas, in H441 cells whose AhR gene was silenced with AhR siRNA, the lack of omeprazole-mediated protective effects
Acknowledgments
This work was supported by grants from the Division of Neonatal–Perinatal Medicine, Texas Children's Hospital, to B.S. and the National Institutes of Health (ES-009132, HL-070921, HL-087174, and ES-019689) to B.M. We thank Esther Inman for providing technical assistance for the completion of this article.
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