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) pl ays an important role in various reproductive functions, including ovu lation, implantation and parturition, and that the local concentration of PAF is modulated by PAF-acetylhydrolase (PAF-AH), a potent PAF ina ctivator. In this study, we investigated the possible effects of vario us bioactive substances, which are present at high concentrations in t he human pregnant uterus, on PAF-AH secretion from decidual macrophage s 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 s ecreted PAF-AH into the culture medium time-and dose-dependently. Afte r treatment with 10(-8) M TPA, the effects of various substances on th e secretion of PAF-AH were examined. Among the substances examined, co rtisol and TGF-beta suppressed PAF-AH secretion from TPA-stimulated HL -60 cells in a significant and dose-dependent way. Endothelin, epiderm al growth factor, and brain natriuretic peptide had no significant eff ect 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 subs tances may play a role in the initiation of parturition via regulation of local PAF concentrations.