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: Roberta Migale, Bronwen R Herbert, Yun S Lee, Lynne Sykes, Simon N Waddington, Donald Peebles, Henrik Hagberg, Mark R Johnson, Phillip R Bennett, David A MacIntyre
• Journal: The American journal of pathology (Am J Pathol) Vol. 185 Issue 9 Pg. 2390-401 (Sep 2015) ISSN: 1525-2191 [Electronic] United States
• PMID: 26212908 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Lipopolysaccharides
• Transcription Factor AP-1

Topics

• Animals
• Disease Models, Animal
• Escherichia coli (drug effects)
• Female
• Inflammation (chemically induced, complications)
• Lipopolysaccharides (pharmacology)
• Mice
• Myometrium (drug effects, metabolism)
• Obstetric Labor, Premature (chemically induced)
• Pregnancy
• Pregnancy Complications (chemically induced)
• Premature Birth (metabolism)
• Transcription Factor AP-1 (metabolism)