EICOSANOID FORMATION IN PULMONARY EPITHELIAL CELLS

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The airway epithelium plays an important role in the inflammatory role of the lung by the formation of bioactive molecules such as eicosanoids. The epithelium serves as an air-liquid barrier for the trachea and bronchi and is a source of secretions including mucin. Retinoids are essential for maintaining the muco-cilliary phenotype. The absence of retinoids leads to squamous metaplasia which is observed in several lung diseases. Muco-cilliary cells produced high levels of PGE2, Express high levels of cPLA2 and PGHS-2. The air-liquid interface system has been successfully extended to human bronchial epithelial cells. The human cells poorly metabolize arachidonic acid to prostaglandins in contrast to the rat cells. In the absence of retinoids, 15-Lipoxygenase and PGHS-2 were not detected. With retinoids, these cells differentiate to muco-cilliary cells and Western and Northern analysis indicated the presence of high levels of the 15-lipoxygenase. Incubation in IL-4 dramatically furthers the increase in expression of 15-LO with no effect on COX-2 expression. IL-4 also inhibited mucin secretion with a time course which suggests 15-LO may down regulate mucin secretion. However, additional experiments are required to determine if 15-LO modulates mucin secretion. These studies indicate an importance of 15-Lipoxygenase in human lung inflammatory responses.