Abstract
Background and Aims
Platelet activating factor (PAF), a potent phospholipid mediator, has been implicated in a number of reproductive processes through ovulation to parturition. To clarify the regulatory mechanism of PAF metabolism in the decidua, we have investigated the effect of activation of protein kinase C (PKC) on the secretion of PAF-acetylhydrolase (PAF-AH), a PAF-inactivating enzyme, by human decidual macrophages.
Methods
Decidual macrophage populations were isolated from human decidua by using enzymic digestion, Ficoll-Paque centrifugation, or flow cytometric sorting. The cells were treated with a PKC activator (TPA), H-7, dibutyryl cyclic adenosine monophosphate (AMP), Bis-(o-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid, tetra (acetoxymethyl)-ester (BAPTA/AM) and/or nifedipine. The activity of PAF-AH secreted in the culture medium was assayed.
Results
The PKC activator, TPA, inhibited the PAF-AH secretion by decidual cells in a dose-dependent manner. The TPA also decreased the enzyme secretion by flow cytometrically purified macrophages. The inhibitory effect of TPA was blocked by a PKC inhibitor, H-7. Protein kinase A (PKA) activation by dibutyryl cyclic AMP was without effect on the enzyme secretion. Calcium channel blockers, BAPTA/AM and nifedipine had no effect on the PAF-AH secretion.
Conclusion
It is suggested that the TPA-induced inhibition of PAF-AH secretion may be mediated, in part, by a PKC-dependent signal transduction, and that activation of PKC may result in the increase in the local concentration of PAF in the decidua because of its inhibitory effect on the PAF-AH secretion by decidual macrophages.
Similar content being viewed by others
References
Narahara H, Frenkel RA, Johnston JM. The role of PAF in reproductive biology. In: Gross R, ed.Advances in Lipobiology. Greenwich: JAI Press, 1996; 241–271.
Billah MM, Johnston JM. Identification of phospholipid platelet-activating factor (1-O-alkyI-2-acetyl-sn-glycero-3-phosphocholine) in human amniotic fluid and urine.Biochem Biophys Res Commun 1983;113: 51–58.
Nishihira J, Ishibashi T, Mai Y, Muramatsu T. Mass spectrometric evidence for the presence of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in human amniotic fluid during labor.Lipids 1984;19: 907–910.
Billah MM, DiRenzo GC, Ban Cet al. Platelet-activating factor metabolism in human amnion and the responses of this tissue to extracellular platelet-activating factor.Prostaglandins 1985;30: 841–850.
Morris C, Khan H, Sullivan MHF, Elder MG. Effects of platelet-activating factor on prostaglandin E2 production by intact fetal membranes.Am J Obstet Gynecol 1992;166: 1228–1231.
Zhu Y-P, Word RA, Johnston JM. The presence of plateletactivating factor binding sites in human myometrium and their role in uterine contraction.Am J Obstet Gynecol 1992;166: 1222–1228.
Sugano T, Nasu K, Narahara H, Kawano Y, Nishida Y, Miyakawa I. Platelet-activating factor induces an imbalance between matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 expression in human uterine cervical fibroblasts.Biol Reprod 2000;62: 540–546.
Sugano T, Narahara H, Nasu K, Arima K, Fujisawa K, Miyakawa I. Effects of platelet-activating factor on cytokine production by human uterine cervical fibroblasts.Mol Hum Reprod 2001;7: 475–481.
Prescott SM, Zimmerman GA, Stafforini DM, McIntyre TM. Platelet-activating factor and related lipid mediators.Ann Rev Biochem 2000;69: 419–445.
Maki N, Hoffman DR, Johnston JM. PAF (platelet-activating factor) acetylhydrolase activities in maternai, fetal, and newborn rabbit plasma during pregnancy and lactation.Proc Natl Acad Sci USA 1988;85: 728–732.
Narahara H, Frenkel R, Johnston JM. Secretion of plateletactivating factor acetylhydrolase (PAF-AH) following phorbol ester-stimulated differentiation of HL-60 cells.Arch Biochem Biophys 1993;301: 275–281.
Narahara H, Nishioka Y, Johnston JM. Secretion of plateletactivating factor acetylhydrolase by human decidual macrophages.J Clin Endocrinol Metab 1993;77: 1258–1262.
Narahara H, Johnston JM. Effects of endotoxins and cytokines on the secretion of platelet-activating factoracetylhydrolase by human decidual macrophages.Am J Obstet Gynecol 1993;169: 531–537.
Narahara H, Miyakawa I, Johnston JM. The inhibitory effect of 1,25-dihydroxyvitamin D3 on the secretion of platelet-activating factor acetylhydrolase by human decidual macrophages.J Clin Endocrinol Metab 1995;80: 3121–3126.
Narahara H, Mine S, Kawano Y, Johnston JM, Miyakawa I. Effects of colony-stimulating factors on the secretion of platelet-activating factor acetylhydrolase by human decidual macrophages.Am J Obstet Gynecol 2003;188: 157–161.
Miwa M, Miyake T, Yamanaka Tet al. Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children.J Clin Invest 1988;82: 1983–1991.
Nishizuka Y. Studies and perspectives of protein kinase C.Science 1986;233: 305–312.
Chao W, Olson MS. Platelet-activating factor: receptors and signal transduction.Biochem J 1993;292: 617–629.
Ruch RJ, Trosko JE, Madhukar BV. Inhibition of connexin43 gap junctional intercellular communication by TPA requires ERK activation.J Cell Biochem. 2001;83: 163–169.
Braquet P, Touqui L, Shen TY, Vargaftig BB. Perspectives in platelet-activating factor research.Pharmacol Rev 1987;39: 97–146.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Narahara, H., Utsunomiya, H., Nishida, M. et al. Activation of protein kinase C inhibits the secretion of platelet-activating factor acetylhydrolase by human decidual macrophages. Reprod Med Biol 2, 121–126 (2003). https://doi.org/10.1046/j.1445-5781.2003.00032.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1046/j.1445-5781.2003.00032.x