Nl. Brown et al., Regulation of prostaglandin production in intact fetal membranes by interleukin-1 and its receptor antagonist, J ENDOCR, 159(3), 1998, pp. 519-526
There is strong evidence for the involvement of inflammatory mediators such
as interleukin (IL)-1 in the biochemical mechanisms of parturition. Theref
ore the effects of the IL-1. family (IL-1 alpha (1 ng/ml), IL-1 beta (1 ng/
ml) and the IL-1 receptor antagonist (IL-1ra) (10 ng/ml)) on the regulation
of prostaglandin synthesis in term human fetal membranes were investigated
. It was found that, after 4 h of culture, IL-1 beta increased prostaglandi
n E-2 (PGE(2)) output approximately twofold. This was associated with both
a significant increase in cyclo-oxygenase-2 (COX-2) mRNA levels (approximat
ely fourfold compared with control) and translocation of cytoplasmic phosph
olipase A(2) (cPLA(2)) from the cytosol to the membrane fraction. IL-1 alph
a was less effective than IL-1 beta at stimulating PGE(2) production throug
h similar mechanisms.
IL-1ra had no effect on PGE(2) output. However, in combination treatments,
IL-1ra did not inhibit IL1 alpha- or IL-1 beta-stimulated PGE(2) output, an
d increased PGE(2) production further compared with IL-1 beta alone. IL-1ra
decreased IL-1 beta-induced COX-2 mRNA expression by about half and signif
icantly increased cPLA(2) protein levels, as detected by immunoblotting, wh
en used alone and together with IL-1 beta. These results suggest that IL-1r
a has partial agonist properties when used together with IL-1 alpha and IL-
1 beta in fetal membranes by increasing cPLA(2) protein levels, which leads
to an increase in the production of prostaglandins.