NAD(P)H Quinone Oxidoreductase 1 Is Essential for Ozone-Induced Oxidative Stress in Mice and Humans

• DOI: 10.1165/rcmb.2008-0381oc
• Publication Date: 2008-12-05T02:54:36Z
• Authors: Judith A. Voynow; Bernard M. Fischer; Shuo Zheng; Erin N. Potts; Amy R. Grover; Anil K. Jaiswal; Andrew J. Ghio; W. Michael Foster
• Keywords: Isoprostanes

One host susceptibility factor for ozone identified in epidemiologic studies is NAD(P)H quinone oxidoreductase 1 (NQO1). We hypothesized that after exposure, NQO1 required to increase 8-isoprostane (also known as F(2)-isoprostane) production, a recognized marker of ozone-induced oxidative stress, and enhance airway inflammation hyperresponsiveness. In this report, we demonstrate contrast wild-type mice, NQO1-null mice are resistant have blunted responses, including decreased production F(2)-isoprostane keratinocyte chemokine, inflammation, diminished Importantly, these results correlate with vitro findings humans. primary human epithelial cells, inhibition by dicumarol blocks IL-8 gene expression. Together, modulates cellular redox status influences the biologic physiologic effects ozone.