Regulation of prostaglandin production in intact fetal membranes by interleukin-1 and its receptor antagonist

Abstract

There is strong evidence for the involvement of inflammatory mediators such as interleukin (IL)-1 in the biochemical mechanisms of parturition. Therefore the effects of the IL-1 family (IL-1 (1 ng/ml), IL-1 (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 increased prostaglandin E 2 (PGE 2 ) output approximately twofold. This was associated with both a significant increase in cyclo-oxygenase-2 (COX-2) mRNA levels (approximately fourfold compared with control) and translocation of cytoplasmic phospholipase A 2 (cPLA 2 ) from the cytosol to the membrane fraction. IL-1 was less effective than IL-1 at stimulating PGE 2 production through similar mechanisms.IL-1ra had no effect on PGE 2 output. However, in combination treatments, IL-1ra did not inhibit IL-1 -or IL-1 -stimulated PGE 2 output, and increased PGE 2 production further compared with IL-1 alone. IL-1ra decreased IL-1 -induced COX-2 mRNA expression by about half and significantly increased cPLA 2 protein levels, as detected by immunoblotting, when used alone and together with IL-1 . These results suggest that IL-1ra has partial agonist properties when used together with IL-1 and IL-1 in fetal membranes by increasing cPLA 2 protein levels, which leads to an increase in the production of prostaglandins.

Macrophages Infiltrate the Human and Rat Decidua During Term and Preterm Labor: Evidence That Decidual Inflammation Precedes Labor1

“…This is consistent with a relatively conservative 3-fold increase in neutrophil chemotactic potential of fetal membranes following labor [14], reinforcing the relative importance of macrophages in the labor process. Infiltration of macrophages may be a trigger for decidual activation due to their production of proinflammatory cytokines (e.g., tumor necrosis factor-a [TNF-a], interleukin [IL]-1b and IL6), and prostaglandins [15][16][17]. Moreover, decidual leucocytes may activate the tissues via paracrine actions of inflammatory mediators, resulting in amplification of leucocyte recruitment through upregulation of chemokines, and elevated production of labor-associated factors MMPs and prostaglandins, resulting in myometrial activation and fetal membrane rupture [16,18,19].…”

Differential activation of mitogen activated protein kinases and nuclear factor-κB in lipopolysaccharide-treated term and preterm amnion cells

“…The severity of the fetal inflammatory response correlates with the levels of proinflammatory cytokines such as IL-1β, IL-6, and IL-8 in fetal plasma, with major perinatal morbidities and also with the severity of placental inflammation [14,24,26]. The cytokines subsequently activate matrix metalloproteinases (MMPs) and prostaglandin E 2 (PGE 2 ), which exert important effects on the degradation of extracellular matrix (ECM) and induce stimulation of preterm labor [4,5,1,21,32]. We have recently shown that the inflammatory response to intrauterine infection is more severe in preterm than in term fetuses.…”

Fetal-Placental and Decidual-Placental Units: Role of Endocrine and Paracrine Regulations in Parturition

“…Moreover, we have already seen that IL-1ß stimulates cPLA2 synthesis and activity and PGE2 release by amnion WISH cells [72]. More precisely, Brown et al [108] showed that IL-1ß increased PGE2 output by intact fetal membranes about 2-fold, and COX-2 mRNA levels about 4-fold compared with controls; IL-1ß also significantly increased translocation of cPLA2 from the cytosol to the plasmic membrane.…”