Abstract
Our recent work has suggested that anti-inflammatory glucocorticoids produce cleft palate in mice by the same biochemical pathway as utilized in their anti-inflammatory action. This pathway includes a glucocorticoid receptor mediated induction of phospholipase A2-inhibitory proteins (PLIP) which inhibit the release of the prostaglandin precursor fatty acid, arachidonic acid, from membrane phospholipids at the level of phospholipase A2, which in turn leads to a subsequent inhibition of prostaglandin production. In this report we have prepared and partially purified such PLIPs of molecular weight about 55,000, 40,000, 28,000, and 15,000 from A/J mouse thymus and from 12-day embryonic B10.A palates. Sufficient quantities of calf thymus PLIP and of the 15,000 molecular weight mouse thymus and palate PLIPs were prepared and tested as inhibitors of programmed cell death in the medial edge epithelium of single mouse embryonic palatal shelves in culture. This event is completely prevented by the inclusion of nanomolar quantities of cortisone in the culture medium. All 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 suggesting that PLIP mediates the effects of glucocorticoids by inhibiting phospholipase A2 (PLA2).
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Goldman, A., Gupta, C., Herold, R. et al. GLUCOCORTICOID-INDUCED PHOSPHOLIPASE A2-INHIBITORY PROTEINS (PLIP) MEDIATE GLUCOCORTICOID TERATOGENICITY IN VITRO. Pediatr Res 18 (Suppl 4), 305 (1984). https://doi.org/10.1203/00006450-198404001-01270
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DOI: https://doi.org/10.1203/00006450-198404001-01270