Human bronchial epithelial cells can initiate, amplify, and attenuate airway inflammatory events through the production of pro- and anti-inflammatory molecules. Examples of pro-inflammatory human bronchial epithelial cell products include interleukins, chemokines, colony-stimulating factors, lipid mediators, nitric oxide, adhesion molecules, and neuropeptides. Examples of anti-inflammatory products include soluble tumor necrosis factor receptors, interleukin (IL)-1 receptor antagonists, IL-10, and protease inhibitors. Since human airway epithelial cells participate in the regulation of inflammatory events, studies have been initiated to identify novel human airway epithelial cell genes that are involved in this regulation. Using differential display reverse transcription- polymerase chain reaction, candidate genes will be identified from a human pulmonary epithelial cell line following stimulation with either pro-inflammatory or anti-inflammatory mediators. After cloning and sequencing candidate genes, studies will be undertaken to identify the genes function as well as factors that regulate their expression. These studies will provide increased understanding of the mechanisms by which human airway epithelial cells modulate inflammatory processes in the airway microenvironment. Identification of novel human airway epithelial cell genes may also allow for new therapeutic approaches to reduce airway inflammation in disorders such as asthma.
