Glucocorticoid-induced phospholipase A2-inhibitory proteins mediate glucocorticoid teratogenicity in vitro.

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Abstract
Dexamethasone induces the synthesis of a phospholipase A2-inhibitory protein (PLIP) of MW .apprxeq. 55,000 from calf thymus and PLIP of MW 55,000, 40,000, 28,000 and 15,000 from A/J mouse thymus and from 12-day embryonic B10.A mouse palates. Sufficient quantities of calf thymus PLIP and of the 15,000 MW mouse thymus and palate PLIP were prepared and tested as inhibitors of programmed cell death in the medial-edge epithelium of single mouse embryonic palatal shelves in culture. All of the proteins tested prevent the loss of the medial-edge epithelium and, thus, produce the teratogenic effects of glucocorticoids in the palatal culture model. This teratogenic action of both PLIP and glucocorticoids is reversed by arachidonic acid, the precursor of prostaglandins and thromboxanes, suggesting that PLIP mediates the effects of glucocorticoids by inhibiting phospholipase A2.