15-Deoxy-Δ12,14-Prostaglandin J2 and Troglitazone Regulation of the Release of Phospholipid Metabolites, Inflammatory Cytokines and Proteases from Human Gestational Tissues

Phospholipid-derived mediators, inflammatory cytokines and extracellular matrix remodelling enzymes are all involved in the initiation of human labour and delivery. We have previously demonstrated that natural and synthetic PPAR-γ ligands regulate LPS-stimulated pro-inflammatory cytokine release from human gestational tissues, however, the effect of these ligands on the basal and/or LPS-induced expression of prostaglandins and proteases is not known. Therefore, the aim of this study was to determine the effects of 15d-PGJ2 and troglitazone on the expression of basal and LPS-stimulated inflammatory mediators in human gestational tissues. Human placenta, amnion and choriodecidua (n = 5) were incubated in the presence or absence of 15 μM 15d-PGJ2 and 30 μM troglitazone under basal and LPS-stimulated (10 μg/ml) conditions. Treatment of placenta, amnion and choriodecidua with both 15d-PGJ2 and troglitazone decreased basal and LPS-stimulated IL-1β, IL-6, IL-10 and TNF-α release. Basal type II PLA2 release from placental tissues was also significantly decreased by 15d-PGJ2 and troglitazone. There was no effects of 15d-PGJ2 and troglitazone on cPLA2 protein expression. Both 15d-PGJ2 and troglitazone significantly decreased basal and LPS-stimulated PGE2 and PGF2α release from placenta and amnion. However, in choriodecidua, although 15d-PGJ2 decreased basal and/or LPS-stimulated PGE2 and PGF2α release, there was an increase in PGE2 and PGF2α release in the presence of troglitazone. 15d-PGJ2 and troglitazone inhibited MMP-9 release from human amnion. NF-κB DNA binding activity and NF-κB p65 protein expression was inhibited by treatment with 15d-PGJ2 in human amnion. There was no effect of 15d-PGJ2 or troglitazone on PPAR-γ protein, and GW9662 failed to alleviate 15d-PGJ2 and troglitazone inhibition of IL-6 and TNF-α release in placenta, amnion and choriodecidua. The data demonstrated in this study suggest that the 15d-PGJ2 and troglitazone exhibit anti-inflammatory properties in human gestational tissues via PPAR-γ independent actions.