title: Specific Lipopolysaccharide Serotypes Induce Differential Maternal and Neonatal Inflammatory Responses in a Murine Model of Preterm Labor.
abstract: Intrauterine inflammation is recognized as a key mediator of both normal and preterm birth but is also associated with neonatal neurological injury. Lipopolysaccharide (LPS) is often used to stimulate inflammatory pathways in animal models of infection/inflammation-induced preterm labor; however, inconsistencies in maternal and neonatal responses to LPS are frequently reported. We hypothesized that LPS serotype-specific responses may account for a portion of these inconsistencies. Four different Escherichia coli LPS serotypes (O111:B4, O55:B5, O127:B8, and O128:B12) were administered to CD1 mice via intrauterine injection at gestational day 16. Although control animals delivered at term 60 ± 15 hours postinjection (p.i.), those administered with O111:B4 delivered 7 ± 2 hours p.i., O55:B5 delivered 10 ± 3 hours p.i., O127:B8 delivered 16 ± 10 hours p.i., and O128:B12 delivered 17 ± 2 hours p.i. (means ± SD). A correlation between the onset of preterm labor and myometrial activation of the inflammatory transcription factor, activator protein 1, but not NF-κB was observed. Specific LPS serotypes induced differential activation of downstream contractile and inflammatory pathways in myometrium and neonatal pup brain. Our findings demonstrate functional disparity in inflammatory pathway activation in response to differing LPS serotypes. Selective use of LPS serotypes may represent a useful tool for targeting specific inflammatory response mechanisms in these models.
authors.affiliation: Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
authors.forename: Roberta
authors.initials: R
authors.lastname: Migale
authors.affiliation: Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom; Academic Department of Obstetrics and Gynaecology, Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: Bronwen R
authors.initials: BR
authors.lastname: Herbert
authors.affiliation: Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
authors.forename: Yun S
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
authors.forename: Lynne
authors.initials: L
authors.lastname: Sykes
authors.affiliation: Gene Transfer Technology Group, Institute for Women's Health, University College London, London, United Kingdom; Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witswatersrand, Johannesburg, South Africa.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Waddington
authors.affiliation: UCL Centre for Perinatal Brain Protection & Repair, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Donald
authors.initials: D
authors.lastname: Peebles
authors.affiliation: Department of Clinical Sciences, Perinatal Center, University of Gothenburg, Gothenburg, Sweden; Division of Imaging Sciences and Biomedical Engineering, Centre for the Developing Brain, King's College London, King's Health Partners, St. Thomas' Hospital, London, United Kingdom.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hagberg
authors.affiliation: Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom; Academic Department of Obstetrics and Gynaecology, Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Johnson
authors.affiliation: Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Bennett
authors.affiliation: Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom. Electronic address: d.macintyre@imperial.ac.uk.
authors.forename: David A
authors.initials: DA
authors.lastname: MacIntyre
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000150:complications; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000139:chemically induced*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced; D047928:Premature Birth / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D018808:Transcription Factor AP-1