title: Apelin is decreased with human preterm and term labor and regulates prolabor mediators in human primary amnion cells.
abstract: A critical role of proinflammatory mediators including cytokines, prostaglandins, and extracellular matrix remodeling enzymes in the processes of human labor and delivery, at term and preterm, has been demonstrated. In nongestational tissues, apelin plays an important role in a number of physiologic processes, including the regulation of inflammation. However, the role and regulation of apelin and the apelin receptor (APJ) in human gestational tissues are not known. The aims of this study were to determine the effect of (i) preterm and term labor on apelin and APJ expression in human gestational tissues and (ii) apelin small interfering RNA (siRNA) knockdown in human primary amnion cells on prolabor mediators. Human placenta and fetal membranes were collected from term nonlaboring women and women after spontaneous labor and delivery. Preterm and term spontaneous labor were associated with significantly lower apelin expression in fetal membranes. On the other hand, there was no effect of labor on APJ expression and no effect of term labor on placental apelin or APJ expression. Transfection of primary amnion cells with apelin siRNA was associated with significantly increased interleukin (IL)-1β-induced IL-6 and IL-8 release and cyclooxygenase-2 messenger RNA (mRNA) expression and resultant prostaglandin E2 and prostaglandin F2α release. There was no effect of apelin siRNA on matrix metalloproteinase (MMP)-9 mRNA expression and pro MMP-9 release. In summary, human labor downregulates apelin expression in human fetal membranes. Furthermore, a role of apelin in the regulation of proinflammatory and prolabor mediators in human fetal membranes is supported by our studies.
authors: Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Level 4/163 Studley Road, Heidelberg, 3084 Victoria, Australia.
authors: Ratana
authors: R
authors: Lim
authors: Gillian
authors: G
authors: Barker
authors: Clyde
authors: C
authors: Riley
authors: Martha
authors: M
authors: Lappas
mesh_terms: D000650:Amnion / Q000378:metabolism*; D000073861:Apelin; D000075244:Apelin Receptors; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D047929:Term Birth / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D015237:Dinoprost; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone
keywords: apelin; cytokines; fetal membranes; human labor; prostaglandins