Human bronchial epithelial cells can initiate, amplify, and attenuate airway inflammatory events via the production of pro- and anti-inflammatory molecules. Examples of proinflammatory 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-1 receptor antagonists, IL-10, and protease inhibitors. Because human airway epithelial cells participate in the regulation of inflammatory events, studies have been initiated to identify novel human airway epithelial cell genes involved in the regulation of airway inflammation. Utilizing differential display RT-polymerase chain reaction, candidate genes will be identified from a human pulmonary epithelial cell line following stimulation with either proinflammatory or anti-inflammatory mediators. Subsequent studies will utilize airway epithelial cells obtained from normal volunteers and volunteers with airway inflammatory disorders, such as asthma. Following the cloning and sequencing of candidate genes, studies will be undertaken to identify their function as well as factors regulating their expression. These studies will provide increased understanding as to the mechanisms by which human airway epithelial cells modulate inflammatory processes in the airway microenvironment. Furthermore, the identification of novel human airway epithelial cell genes may allow for the development of new therapeutic approaches of reducing airway inflammation in disorders such as asthma.
