Effect of prostaglandin E(2) on eicosanoid release by human bronchial biopsy specimens from normal and inflamed mucosa

Background - Eicosanoids such as prostaglandin E(2) (PGE(2)) thromboxane A(2) (TXA(2)), and peptidoleukotrienes (pLT) are known to be biologically highly active lipid mediators, especially in human lung epithelium. PGE(2) is thought to have mostly bronchoprotective effects, whereas pLT and TXA(2) are bronchoconstrictive. This study was undertaken to assess the release and interaction of eicosanoids in human bronchial biopsy specimens of normal and inflamed mucosa. Methods - Bronchial biopsy specimens were obtained from 16 patients, seven controls without signs of inflammation and nine patients with severe inflammatory processes in the epithelium. The release of pLT, TXA(2) (measured as TXB(2)), and PGE(2) was investigated using a ''functional in vitro test'' and the addition of several stimuli. Results - Specimens incubated with arachidonic acid released higher amounts of pLT, TXB(2), and PGE(2) than unstimulated specimens. Preincubation with PGE(2) revealed significant inhibition of arachidonic acid-induced release of pLT and TXB(2) (> 50%). The inhibitory effect was higher in normal than in inflamed epithelium. Conclusions - Exogenous PGE(2) has inhibitory effects on the release of pLT and TXB(2) in human bronchial biopsy specimens. This finding could explain the bronchoprotective effect of inhaled PGE, in normal subjects and asthmatic subjects as direct eicosanoid interactions. It also supports the concept of PGE(2) as a bronchoprotective endogenous substance. The complex effects of PGE(2) as a modulating mediator in inflammation may be worth investigating.