title: A novel antiinflammatory role for the short-chain fatty acids in human labor.
abstract: Human parturition is an inflammatory process that can be activated prematurely by pathological stimuli. This study investigated the expression of G protein-coupled receptors GPR43 and GPR41 receptors in human uteroplacental tissues and the role of short-chain fatty acids (SCFA) in modulating inflammatory pathways in fetal membranes. Expression of GPR43 and GPR41 was investigated in uteroplacental tissues collected from women delivering at term or preterm after ethical approval and patient informed consent. The effect of SCFA on expression of inflammatory genes was assessed in amnion explants after culture with a mimetic of infection (lipopolysaccharide, LPS). Sodium propionate effect on LPS-induced neutrophil chemotaxis was evaluated by transwell assay. GPR43 and GPR41 mRNA expression was higher in myometrium and fetal membranes collected from women after the onset of labor. GPR43 protein expression localized to immune cells and vascular endothelium in the myometrium and epithelium of fetal membranes. Treatment with LPS significantly increased mRNA expression of GPR43 and inflammatory genes. Cotreatment with LPS and sodium propionate decreased LPS-induced expression of inflammatory genes including IL-6, IL-8, cyclooxygenase-2, IL-1α, intercellular adhesion molecule-1, and platelet endothelial cell adhesion molecule-1 but not IL-1β or lymphocyte function-associated antigen-1. Sodium propionate reduced LPS-induced neutrophil chemotaxis and protein secretion of the neutrophil chemoattractant IL-8. Finally, fetal membrane expression of GPR43 was significantly higher in women delivering preterm with evidence of infection. GPR43-SCFA interactions may represent novel pathways that regulate inflammatory processes involved in human labor. Suppression of inflammatory pathways by SCFA may be therapeutically beneficial for pregnant women at risk of pathogen-induced preterm delivery.
authors.affiliation: Medical Research Council Human Reproductive Sciences Unit, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom. voltolini2@unisi.it
authors.forename: Chiara
authors.initials: C
authors.lastname: Voltolini
authors.forename: Sharon
authors.initials: S
authors.lastname: Battersby
authors.forename: Sophie L
authors.initials: SL
authors.lastname: Etherington
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
authors.forename: Jane E
authors.initials: JE
authors.lastname: Norman
authors.forename: Henry N
authors.initials: HN
authors.lastname: Jabbour
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D005321:Extraembryonic Membranes / Q000187:drug effects / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000502:physiology*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007743:Labor, Obstetric / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D007752:Obstetric Labor, Premature / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011422:Propionates / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D005232:Fatty Acids, Volatile; D018836:Inflammation Mediators; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011422:Propionates; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C508606:CXCL8 protein, human; C473103:FFAR2 protein, human; C106262:FFAR3 protein, human; C514135:sodium propionate