Cyclic stretch inhibits prostacyclin secretion by airway epithelial cells

Metabolites of arachidonic acid (AA) have been proposed to play an important role in airway diseases such as asthma and chronic obstructive disorders. In airway epithelium, AA is metabolized to a variety of prostanoids via cyclooxygenase (COX). Some products such as prostacyclin (PGI2) and prostaglandin E2 (PGE2) are bronchoprotective, while others such as thromboxane A2 (TxA2) are bronchoconstrictive. Since obstruction can lead to changes in the distension of airways, we investigated whether cyclic stretch influenced production of these COX products. Primary cat trachéal epithelial cells (CTE) and a cell line of airway epithelial cells derived from a human lung adenocarcinoma (Calu 3) were grown to confluence on flexible silastic membranes and subjected to cyclic stretch (20% strain) by applying an oscillating vacuum (Flexercell Intl.). Samples were processed for 6-keto-PGF-l a (stable metabolite of PGI2) with an EIA kit. After 10 min the amount of PGI2 secreted by stretched cells was 46 to 81% lower than that produced by control cells (n=2, Table 1). The inhibition of PGI2 production was frequency dependent in both Calu 3 and CTE cells, with a greater inhibition observed at 10 cycles/min (cpm). Preliminary measurements also show that stretch at 10 cpm inhibits TxB2 (stable metabolite of TxA2) secretion by 59% and PGE2 secretion by 85%. The inhibition of secretion of these prostanoids indicates regulation of the AA cascade at the level of COX, and may have implications for obstructive airway disease. Supported by The Whitaker Foundation and the Chicai o Lung Association. Table 1 values are pg/1000 cells. control 10 cpm 30 cpm Calu 3 0.225 0.044 0.106 CTE 0.184 0.044 0.109.