Mechanisms of oxidant stress sensing in a model human airway epithelial cell line.

Inflammatory lung diseases are among the world¿s most prevalent diseases whose incidence, and consequent cost to society, are increasing. One factor common to all inflammatory lung diseases is the presence of reactive oxygen species (ROS) and the epithelial cells lining the lungs are particularly vulnerable to ROS-mediated damage. This proposal will investigate how one cell type in the lung, which is important in controlling fluid and salt secretion, functions under conditions of oxidant stress. I have previously reported that the ROS hydrogen peroxide, and an example of a class of compound (called isoprostanes) generated when hydrogen peroxide reacts with cell membranes, stimulate secretion from a type of airway epithelial cell (Calu-3 cells). This proposal seeks to understand at the molecular and functional level, how isoprostanes achieve there effects on Calu-3 cells; how much of the reponse to hydrogen peroxide is due to isoprostane generation; and finally whether ROS exposure results in adaptive changes within these cells. Understanding how exposure to oxidant stress affects airway epithelial cells is an important first step in reducing ROS-mediated damage to the lungs, and may ultimately help prevent reduce the severity of inflammatory lung diseases.