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.

IL-1 receptor antagonist therapy mitigates placental dysfunction and perinatal injury following Zika virus infection

“…We and others (11) hypothesize that the placental inflammation during ZIKV infection may contribute significantly to adverse perinatal outcomes, and should be considered in therapeutic approaches for ZIKV and other infections that cause congenital defects during pregnancy. The maternal inflammatory response represents an environmental factor that is known to increase the risk for childhood and developmental diseases (51,52), such as autism spectrum disorders, schizophrenia, learning disabilities, as well as cognitive and motor deficits (53)(54)(55). Although ZIKV infection has direct effects on fetal tissues, we show that placental inflammation is also a major contributor to adverse perinatal outcomes following in utero ZIKV infection.…”

Short-Term versus Long-Term Culture of A549 Cells for Evaluating the Effects of Lipopolysaccharide on Oxidative Stress, Surfactant Proteins and Cathelicidin LL-37

“…However, many research groups use different LPS serotypes or LPS from different bacteria and many of them do not specify LPS serotype. It has been shown that LPS substructures could modulate its endotoxic properties, possibly by different interactions of the LPS molecule with the TLR4 receptor complex, leading to different activation of subsequent inflammatory pathways [38,39]. This is supported by studies which have found that structural differences in O-antigen of LPS molecule are able to modulate its recognition and phagocytosis by macrophages [40,41].…”

Neutrophils Discriminate between Lipopolysaccharides of Different Bacterial Sources and Selectively Release Neutrophil Extracellular Traps

“…Growing evidence supports the notion that inflammatory responses triggered by LPS vary among serotypes. For instance, in a murine model of infection-induced preterm labor, four different E. coli LPS serotypes yielded highly variable outcomes (32). Our data suggest that subtle changes in the sugar composition of the O-antigen can impact NET release in response to LPS.…”