of Work: 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. The major arachidonic acid metabolite was PGE2 for both squamous and muco-cilliary rat phenotypes. Muco-cilliary cells produced high levels of PGE2, express high levels of cPLA2 and PGHS-2, whereas squamous cells produced very low levels of PGHS-2. The PGHS-1 isoform was observed in the squamous but not in the muco-cilliary cells. Recently, the air-liquid interface system used to investigate differentiation of rat tracheal cells into squamous and muco-cilliary phenotype 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 was not detected. With retinoids, these cells differentiate to mucocilliary cells and Western and Northern analysis indicated the presence of high levels of the 15-lipoxygenase. Although arachidonic acid is poorly metabolized by intact cells, linoleic acid is converted extensively to 13(S)-HODE. However, 15-lipoxygenase can metabolize arachidonic acid in cell lysates. These studies indicate an importance of 15-lipoxygenase in human lung inflammatory responses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES050145-03
Application #
6162252
Study Section
Special Emphasis Panel (LMC)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code