Omeprazole attenuates hyperoxic injury in H441 cells via the aryl hydrocarbon receptor

Free Radic Biol Med. 2011 Nov 15;51(10):1910-7. doi: 10.1016/j.freeradbiomed.2011.08.013. Epub 2011 Aug 23.


Hyperoxia contributes to the development of bronchopulmonary dysplasia in premature infants. Earlier we observed that aryl hydrocarbon receptor (AhR)-deficient mice are more susceptible to hyperoxic lung injury than AhR-sufficient mice, and this phenomenon was associated with a lack of expression of cytochrome P450 1A enzymes. Omeprazole, a proton pump inhibitor used in humans with gastric acid-related disorders, activates AhR in hepatocytes in vitro. However, the effects of omeprazole on AhR activation in the lungs and its impact on hyperoxia-induced reactive oxygen species (ROS) generation and inflammation are unknown. In this study, we tested the hypothesis that omeprazole attenuates hyperoxia-induced cytotoxicity, ROS generation, and expression of monocyte chemoattractant protein-1 (MCP-1) in human lung-derived H441 cells via AhR activation. Experimental groups included cells transfected with AhR small interfering RNA (siRNA). Hyperoxia resulted in significant increases in cytotoxicity, ROS generation, and MCP-1 production, which were significantly attenuated with the functional activation of AhR by omeprazole. The protective effects of omeprazole on cytotoxicity, ROS production, and MCP-1 production were lost in H441 cells whose AhR gene was silenced by AhR siRNA. These findings support the hypothesis that omeprazole protects against hyperoxic injury in vitro via AhR activation that is associated with decreased ROS generation and expression of MCP-1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / adverse effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Cytoprotection / drug effects
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Humans
  • Hyperoxia / drug therapy*
  • Hyperoxia / pathology
  • Hyperoxia / physiopathology
  • Lung / pathology
  • Lung Injury / prevention & control
  • Omeprazole / administration & dosage*
  • Omeprazole / adverse effects
  • Reactive Oxygen Species / metabolism
  • Receptors, Aryl Hydrocarbon / immunology
  • Receptors, Aryl Hydrocarbon / metabolism*


  • Anti-Inflammatory Agents
  • CCL2 protein, human
  • Chemokine CCL2
  • Reactive Oxygen Species
  • Receptors, Aryl Hydrocarbon
  • Omeprazole