Recovery of Human Tracheal Cell Epithelial Cell Cyclooxygenase Following Inactivation

Abstract

Airway epithelium responds to a variety of stimuli and injuries with the production of inflammatory mediators derived from arachidonic acid - - prostaglandins, leukotrienes and HETEs. These mediators are important not only maintaining normal airway function (e.g. regulating vascular tone, ion transport and mucus secretion) but also as a part of the airway inflammatory response. While mobilization of arachidonic acid from membrane lipids is the rate controlling step for prostaglandin biosynthesis acutely in response to stimuli, regulation of cyclooxygenase levels may be an important factor in long term regulation of prostaglandin production. Cyclooxygenase is a “suicidal” enzyme, which inactivates itself during catalysis. It is also inactivated by aspirin-related drugs. Moreover, the the airway is directly exposed to environmental pollutants such as ozone which can lead to cyclooxygenase inactivation. Thus regulation of cyclooxygenase levels may be critical to the ability of the airway epithelium to produce prostaglandins. In this report we present our initial studies on the capacity of human tracheal epithelial cells in culture to recover from inactivation of cyclooxygenase by aspirin or arachidonic acid, and the effects of macromolecule synthesis inhibitors on that recovery.