EFFECT OF FUROSEMIDE ON PROSTAGLANDIN SYNTHESIS BY HUMAN NASAL AND BRONCHIAL EPITHELIAL-CELLS IN CULTURE

Inhaled furosemide protects asthmatic subjects against bronchial obstruction caused by indirect provocants. We have attempted to correlate the protective effect of furosemide with its ability to alter prostaglandin (PG) synthesis by the airway epithelium. Human epithelial cells from nasal polyps and bronchi were cultured in DME-Ham's F12 medium with 10% fetal calf serum. Confluent cells (days 6 through 8) were incubated for 30 min in fresh medium, and the PGs in the supernatant were measured by radioimmunoassay. say. Spontaneous output (ng.ml(-1).mg(-1) cell protein) ws follows (mean +/- SEM): PGE(2) = 7.74 +/- 2.10 (n = 12), PGF(2 alpha) = 1.66 +/- 0.12 (n = 15), 6-keto-PGF(1 alpha) = 4.32 +/- 1.37 (n = 11), PGD(2) = 0.73 +/- 0.16 (n = 11) for bronchial cells and PGE(2) = 7.24 +/- 0.80 (n = 32), PGF(2a) = 1.38 +/- 0.12 (n = 17), 6-keto-PGF(1 alpha) = 6.79 +/- 2.50 (n = 15), PGD(2) = 0.42 +/- 0.07 (n = 17) for nasal cells. Incubation with arachidonic acid (25 mu/ml) for 30 min significantly increased the amounts of the four PGs. Incubation with furosemide (10(-4) M) for 30 min caused a marked reduction in both basal and arachidonic acid-stimulated production of PGE(2) and PGF(2 alpha) but did not reduce production of 6-keto-PGF(1 alpha) and PGD(2). Incubation with bumetanide (10(-4) M) for 30 min did not modify the PGE(2) synthesis by nasal epithelial cells. The differential effects of furosemide on PG production by primary cultures of human airway epithelial cells might be best explained by inhibition of PGH-9-keto-isomerase and PGH-PGF(2 alpha) reductase. Because PGE(2) potentiates the effects of inflammatory mediators in airways through its vasodilator effect on the tracheobronchial circulation, and because PGF(2 alpha) is a mild bronchoconstrictor agent, our results suggest that inhaled furosemide might protect asthmatic subjects against indirect provocants by decreasing the production of these PGs by airway epithelial cells.