Cortisol and TGF-beta inhibit secretion of platelet-activating factor- acetylhydrolase secretion in a monocyte-macrophage model system

Recent studies have suggested that platelet activating factor (PAF) playsan important role in various reproductive functions, including ovulation,implantation and parturition, and that the local concentration of PAF ismodulated by PAF-acetylhydrolase (PAF-AH), a potent PAF inactivator. Inthis study, we investigated the possible effects of various bioactivesubstances, which are present at high concentrations in the human pregnantuterus, on PAF-AH secretion from decidual macrophages using amonocyte-macrophage model system, human myelocytic leukaemia cells (HL-60).By treatment with 12-O- tetradecanoylphorbol-13-acetate (TPA), HL-60 cellswere transformed to macrophage-like cells, which secreted PAF-AH into theculture medium time- and dose-dependently. After treatment with 10(-8) MTPA, the effects of various substances on the secretion of PAF-AH wereexamined. Among the substances examined, cortisol and TGF-beta suppressedPAF-AH secretion from TPA-stimulated HL-60 cells in a significant and dose-dependent way. Endothelin, epidermal growth factor, and brain natriureticpeptide had no significant effect on PAF-AH secretion from TPA-stimulatedHL-60 cells. These results suggest that local PAF concentrations in thepregnant uterus might be regulated, at least partly, by cortisol andTGF-beta; thus these substances may play a role in the initiation ofparturition via regulation of local PAF concentrations.