Prevention of preterm labour via the modulation of inflammatory pathways

MacIntyre, David A.; Sykes, Lynne; Teoh, Tiong Ghee; Bennett, Phillip R.

doi:10.3109/14767058.2012.666114

Cited by 63 publications

(53 citation statements)

References 27 publications

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“…Numerous pathways culminate in preterm birth, including infection and/or inflammation (MacIntyre et al, 2012). The development of therapeutics to manage and prevent preterm labour can only arise from a complete understanding of the role of inflammation in initiating uterine contractions and membrane rupture.…”

Section: Discussionmentioning

confidence: 99%

Slit2 is decreased after spontaneous labour in myometrium and regulates pro-labour mediators

Lim

Liong

Barker

et al. 2014

Journal of Reproductive Immunology

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Preterm birth, a global healthcare problem, is commonly associated with inflammation. As Slit2 plays an emerging role in inflammation, the purpose of this study was to determine the effect of Slit2 on labour mediators in human gestational tissues. Slit2 mRNA and protein expression were assessed using qRT-PCR and immunohistochemistry in foetal membranes and myometrium obtained before and after labour. Slit2 silencing was achieved using siRNA in primary myometrial cells. Pro-inflammatory and pro-labour mediators were evaluated by qRT-PCR, ELISA and gelatin zymography. Slit2 mRNA and protein expression were found to be significantly lower in myometrium after labour onset. There was no effect of term or preterm labour on Slit2 expression in foetal membranes. Slit2 mRNA expression was decreased in myometrium treated with LPS and IL-1β. Slit2 siRNA in myometrial cells increased IL-1β-induced pro-inflammatory cytokine gene expression and release (IL-6 and IL-8), COX-2 expression and prostaglandin PGE2 and PGF2α release, and MMP-9 gene expression and pro MMP-9 release. There was no effect of Slit2 siRNA on IL-1β-induced NF-κB transcriptional activity. Our results demonstrate that Slit2 is decreased in human myometrium after labour and our knock-down studies describe an anti-inflammatory effect of Slit2 in myometrial cells.

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Section: Discussionmentioning

confidence: 99%

Slit2 is decreased after spontaneous labour in myometrium and regulates pro-labour mediators

Lim

Liong

Barker

et al. 2014

Journal of Reproductive Immunology

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“…4,5 An increasing body of evidence supports the involvement of inflammation also, in the absence of overt infection, in preterm birth. 2 A key mediator of the inflammatory response in gestational tissues at the time of labor is NF-k light chain enhancer of activated B cells (NF-kB); however, data have also implicated activator protein 1 (AP-1) and CCAAT/enhancer-binding proteins (C/EBPs) in the regulation of inflammatory pathways associated with the onset of labor. 6e9 In various animal models of preterm labor (PTL), the Gram-negative bacterial cell wall component, lipopolysaccharide (LPS), is administered systemically to mimic bacterial infection during pregnancy or locally via an intrauterine injection to reflect ascending vaginal infection and/or chorioamnionitis.…”

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confidence: 99%

“…Evidence from both human and animal studies indicates that activation of inflammatory pathways in gestational tissues is a shared mechanism common to both normal and preterm birth. 2,3 Intrauterine inflammation is also associated with fetal brain injury, which may lead to longterm neurological disorders, such as cerebral palsy. 4,5 An increasing body of evidence supports the involvement of inflammation also, in the absence of overt infection, in preterm birth.…”

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confidence: 99%

Specific Lipopolysaccharide Serotypes Induce Differential Maternal and Neonatal Inflammatory Responses in a Murine Model of Preterm Labor

Migale

Herbert

Lee

et al. 2015

The American Journal of Pathology

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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.

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“…It has also been indicated that maternal diet affects microbes identified at the important maternal-fetal interface of the placenta (85,86). Both preeclampsia and preterm delivery are conditions characterised by disturbed inflammatory responses (87,88). Hence the mechanism for the beneficial effects of certain diets on the risk of preeclampsia and preterm delivery may be through reduced inflammation due to intake of vegetables (24,30,32) and probiotic food (26,29).…”

Section: Possible Explanations For Findings and Comparison With Othermentioning

confidence: 99%

Diet matters, particularly in pregnancy – Results from MoBa studies of maternal diet and pregnancy outcomes

Brantsæter¹,

Haugen²,

Myhre³

et al. 2014

Nor J Epidemiol

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Awareness that maternal diet may influence the outcome of pregnancy as well as the long-term health of mother and child has increased in recent years. A new food frequency questionnaire (FFQ) was developed and validated specifically for the Norwegian Mother and Child Cohort Study (MoBa). The MoBa FFQ is a semi-quantitative tool which covers the average intake of food, beverages and dietary supplements during the first 4 to 5 months of pregnancy. It includes questions about intakes of 255 foods and dishes and was used from 2002 onwards. Data assessed by the MoBa FFQ is available for 87,700 pregnancies. Numerous sub-studies have examined associations between dietary factors and health outcomes in MoBa. The aim of this paper is to summarize the results from 19 studies of maternal diet and pregnancy outcomes, which is the complete collection of studies based on the MoBa FFQ and published before September 2014. The overall research question is whether maternal diet -from single substances to dietary patterns -matters for pregnancy outcome. The pregnancy outcomes studied till now include birth size measures, infants being small and large for gestational age, pregnancy duration, preterm delivery, preeclampsia, as well as maternal gestational weight gain and postpartum weight retention. As a whole, the results from these studies corroborate that the current dietary recommendations to pregnant women are sound and that maternal diet during pregnancy is likely to contribute to reduce the risk of pregnancy complications including preterm birth, preeclampsia, and reduced foetal growth. The results provide supporting evidence for recommending pregnant women to consume vegetables, fruit, whole grain, fish, dairy, and water regularly and lower the intake of sugar sweetened beverages, processed meat products and salty snacks. The results showing negative impact of even low levels of environmental contaminants support the precautionary advice on consumption of foods containing these. New findings are that particularly lean fish explained the positive association between seafood intake and foetal growth, and the indications of a protective effect of probiotic and antimicrobial foods on pregnancy outcomes. This points to the importance of diet composition for a healthy gut flora and the body's immune response. Although these studies are observational and cannot infer causality, the results identify diet as an important modifiable lifestyle factor, suggesting that healthy eating, defined as following the official recommendations, is particularly important in pregnancy.This is an open access article distributed under the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Prevention of preterm labour via the modulation of inflammatory pathways

Cited by 63 publications

References 27 publications

Slit2 is decreased after spontaneous labour in myometrium and regulates pro-labour mediators

Slit2 is decreased after spontaneous labour in myometrium and regulates pro-labour mediators

Specific Lipopolysaccharide Serotypes Induce Differential Maternal and Neonatal Inflammatory Responses in a Murine Model of Preterm Labor

Diet matters, particularly in pregnancy – Results from MoBa studies of maternal diet and pregnancy outcomes

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