1.
Prostaglandin E2 (
PGE2) is thought to be an important inhibitory modulator of inflammatory processes in the airway. It inhibits inflammatory cell function and
cholinergic neurotransmission in vitro and roles have been postulated in vivo in refractoriness and in the mechanism of action of the
diuretic agent,
frusemide. 2. The production of
PGE2 by bovine cultured airway smooth muscle cells has been studied under a range of conditions. The effects of
cyclo-oxygenase inhibitors (
flurbiprofen,
indomethacin, acetyl
salicylic acid) on serum-induced production of
PGE2 were assessed over a range of concentrations (10(-7)-10(-4) M). 3. Serum-stimulated production of
PGE2 in control wells ranged from 350 to 800 ng
PGE2 ml-1 in cells from different animals. All three
cyclo-oxygenase inhibitors inhibited
PGE2 production with an order of potency,
flurbiprofen >
indomethacin > acetyl
salicylic acid. Log IC50 values were -6.24 for
flurbiprofen, -5.23 for
indomethacin and -3.50 for acetyl
salicylic acid. 4.
PGE2 production was stimulated by
arachidonic acid (10(-5) M) or addition of the proinflammatory mediator,
bradykinin (10(-8)-10(-5) M). 5. Incubation of cells for 24 h with 5 bromo
deoxyuridine (
BRDU) (10(-4) M) to prevent
DNA synthesis did not alter
PGE2 production in response to serum, suggesting that it was not a function of proliferation per se. 6. Our study suggests that airway smooth muscle may be an important source of
PGE2. Production of
PGE2 may be a novel feedback mechanism whereby airway smooth muscle cells can negatively modulate airways
inflammation. The differing potencies of the
cyclo-oxygenase inhibitors may explain the contrasting effect of these drugs in recent studies in
asthma.