15-deoxy-Δ12,14-prostaglandin J2-induced apoptosis in amnion-like WISH cells

Apoptosis at the site of rupture has been proposed to play a role in premature rupture of the fetal membranes, a condition associated with increased risk of neonatal sepsis and preterm birth. We investigated the ability of peroxisome proliferator-activated receptor (PPAR)-gamma ligands 15-deoxy-Delta(12,14)PGJ(2) (15d-PGJ(2)), Delta(12)PGJ2(,) ciglitizone and rosiglitazone to induce apoptosis in the amnion-like WISH cell line. 15d-PGJ(2) (10 muM) induced morphological characteristics of apoptosis within 2 h, with biochemical indices (caspase activation and substrate cleavage) following shortly after; maximum cell death (approximately 60%) was observed by 16 h, with an EC50 of approximately 7 muM 15d-PGJ(2). Delta(12)-PGJ(2) also induced apoptosis but was less potent and acted at a much slower rate. While ciglitizone also induced apoptosis, rosiglitazone had no effect on cell viability. The mechanism of induction of apoptosis by 15d-PGJ(2) and Delta(12)PGJ(2), which may be independent of PPAR-gamma activation, requires further elucidation. (C) 2001 Elsevier Science Inc. All rights reserved.