The inhibitory effect of 1,25-dihydroxyvitamin D3 on the secretion of platelet-activating factor acetylhydrolase by human decidual macrophages.
The effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and 25-hydroxyvitamin D3 on the secretion of a platelet-activating factor (PAF)-inactivating enzyme, PAF-acetylhydrolase (PAF-AH), by decidual macrophage populations were examined. 1,25-(OH)2D3 inhibited PAF-AH secretion by either decidual cells or flow cytometrically purified decidual macrophages. 25-Hydroxyvitamin D3 also decreased the enzyme secretion but at higher concentrations than those required for 1,25-(OH)2D3. The 1,25-(OH)2D3-induced inhibition was partially blocked by protein kinase C (PKC) inhibitors, sphingosine and 1-(5-isoquinolinesulfonyl)-2-metylpiperazine (H-7). An intracellular calcium channel blocker, bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl)-ester (BAPTA/AM), also partially blocked the inhibition by 1,25-(OH)2D3, whereas extracellular calcium channel blockers, verapamil and nifedipine, failed to prevent the inhibition. H-7 and BAPTA/AM additively blocked the 1,25-(OH)2D3-induced inhibition. A PKC activator, 12-O-tetradecanoylphorbol 13-acetate, also decreased PAF-AH secretion. The decrease was abolished by sphingosine or H-7. It is suggested that 1,25-(OH)2D3 may increase the concentration of PAF in the decidua via its inhibitory effect on PAF-AH secretion by decidual macrophages and that the inhibitory action may be mediated by intracellular calcium and PKC-dependent signal transduction. PAF and 1,25-(OH)2D3 may, therefore, play a cooperative role in the regulation of PAF metabolism at the maternal-fetal interface.
Narahara
H
H
Department of Obstetrics and Gynecology, Oita Medical University, Japan.
Miyakawa
I
I
Johnston
J M
JM
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D002117:Calcitriol / Q000494:pharmacology*; D002452:Cell Count; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D002117:Calcitriol