Cytokine alteration of epithelial cell function may be an important mechanism by which airway inflammation causes airway disease. Cytosolic phospholipase A2 (cPLA2) is an arachidonate selective enzyme which may be primarily responsible for the release of arachidonate from airway epithelial cells. During the course of this project, the T cell product Interferon-gamma has been found to increase cPLA2 gene expression and protein production. This effect is controlled in part at the transcriptional level. Tumor Necrosis Factor-alpha has also been found to increase cPLA2 expression and to activate the enzyme in respiratory epithelial cells. Leukemia Inhibitory Factor (LIF) receptors have been demonstrated on respiratory epithelial cells and LIF has been shown to increase cPLA2 protein and enzyme activity. In a separate study, neutrophil elastase in nanogram/ml concentrations has been shown capable of inducing cPLA2 enzyme production and activation. Efforts are now directed at assessing transcriptional regulation of cPLA2 gene expression in response to LIF and to elastase stimulation of epithelial cells and to defining signal transduction events and nuclear acting factors important in these responses. Understanding the control of expression of the enzyme in teh respiratory epithelium will hopefully allow for a better understanding of airway inflammation.
