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

Recent studies have suggested that platelet activating factor (PAF) plays an important role in various reproductive functions, including ovulation, implantation and parturition, and that the local concentration of PAF is modulated by PAF-acetylhydrolase (PAF-AH), a potent PAF inactivator. In this study, we investigated the possible effects of various bioactive substances, which are present at high concentrations in the human pregnant uterus, on PAF-AH secretion from decidual macrophages using a monocyte-macrophage model system, human myelocytic leukaemia cells (HL-60). By treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), HL-60 cells were transformed to macrophage-like cells, which secreted PAF-AH into the culture medium time- and dose-dependently. After treatment with 10(-8) M TPA, the effects of various substances on the secretion of PAF-AH were examined. Among the substances examined, cortisol and TGF-beta suppressed PAF-AH secretion from TPA-stimulated HL-60 cells in a significant and dose-dependent way. Endothelin, epidermal growth factor, and brain natriuretic peptide had no significant effect on PAF-AH secretion from TPA-stimulated HL-60 cells. These results suggest that local PAF concentrations in the pregnant uterus might be regulated, at least partly, by cortisol and TGF-beta; thus these substances may play a role in the initiation of parturition via regulation of local PAF concentrations.