The effect of high molecular phospholipase A2 inhibitors on 3T6 fibroblast proliferation.

Recently, we suggested that arachidonic acid and/or its cyclooxygenase pathway metabolites may be involved in regulating 3T6 fibroblast proliferation. In the present study we evaluate the role of high-molecular phospholipase A2 (PLA2) enzymes in the 3T6 fibroblast growth. Our results demonstrate that the cytosolic PLA2 inhibitor, arachidonyl trifluoromethylketone and the cytosolic calcium-independent PLA2 (iPLA2) inhibitor, bromoenol lactone, decrease arachidonic acid release and prostaglandin E2 production in 3T6 fibroblast cultures stimulated by fetal calf serum. These effects were correlated with the impairment of 3T6 fibroblast proliferation and DNA synthesis at the S/G2 boundary, which prolongs the S phase. These data suggest a role of iPLA2 in the control of 3T6 fibroblast growth.