PCB 50 stimulates release of arachidonic acid and prostaglandins from late gestation rat amnion fibroblast cells.
Amniotic phospholipase A2 activity contributes to elevated levels of arachidonic acid and prostaglandins observed during labor. Polychlorinated biphenyls (PCBs) activate PLA2 and have been associated with shortened gestation length. To determine if PCBs stimulate amniotic PLA2, cell cultures of rat amnion fibroblasts (RAF) were established from gestation day (gd) 20 rats and labeled with 0.5 micro Ci [3H]-arachidonic acid prior to a 0.5- or 4-h exposure to 0.1% DMSO (solvent control), PCB 50 (1-50 micro M) or TNFalpha (positive control). PCB 50 and TNFalpha induced significant release of [3H]-arachidonic acid from amnion fibroblast cells in time-dependent manners (p<0.001), an effect associated with a significant increase in iPLA2 expression (p<0.05). PCB 50 also stimulated prostaglandin production from RAF cells independent of changes in immunoreactive COX-2. These data suggest that amnion may serve as a target for PCB-induced release of arachidonic acid and uterotonic prostaglandins, with a potential for adverse pregnancy outcomes.
Brant
Kelly A
KA
Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109-2029, USA. kbrant@umich.edu
Caruso
Rita Loch
RL
D000650:Amnion / Q000166:cytology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005865:Gestational Age; D010741:Phospholipases A / Q000032:analysis / Q000378:metabolism; D054467:Phospholipases A2; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D016718:Arachidonic Acid; D011078:Polychlorinated Biphenyls; D051546:Cyclooxygenase 2; D010741:Phospholipases A; D054467:Phospholipases A2; C447028:2,2',4,6-tetrachlorobiphenyl; D004121:Dimethyl Sulfoxide