Non-infected preterm parturition is related to increased concentrations of IL-6, IL-8 and MCP-1 in human cervix

Törnblom, Susanne Abelin; Klimaviciute, Aurelija; Byström, Birgitta; Chromek, Milan; Brauner, Annelie; Ekman-Ordeberg, Gunvor

doi:10.1186/1477-7827-3-39

Cited by 100 publications

(27 citation statements)

References 60 publications

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“…Previous studies have shown that elevated levels of CRP in amniotic fluid and maternal plasma in the second trimester are strongly associated with spontaneous preterm birth (Wei et al 2010). CRP levels in maternal blood of women at the onset of labour were significantly higher than in women who were not in labour (Tö rnblom et al 2005); this agrees with the results of our DiGE analysis.…”

Section: Emergency Caesarean Sectionsupporting

confidence: 92%

Low abundance plasma proteins in labour

Wang¹,

Heesom²,

Phillips³

et al. 2012

Reproduction

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Every year, millions of births worldwide are complicated by prematurity or difficult post-term deliveries, resulting in a high incidence of perinatal mortality and morbidity. Our poor understanding of human parturition is a key reason for our inability to improve the management of preterm and post-term birth. In this study, we used proteomic techniques to look into protein changes in placental blood plasma obtained from women before or after spontaneous or induced labour, with vaginal or caesarean section deliveries. Our aim was to understand the basic mechanisms of human parturition regardless of whether the signals that trigger labour are of maternal and/or fetal origin. We found proteins from 33 genes with significantly altered expression profiles in relation to mode of labour and delivery. Most changes in labour occurred in proteins associated with 'immune and defence responses'. Although the signal transduction and regulation of these pathways varied among modes of delivery, hepatocyte nuclear factor 1 homeobox A emerged as a shared protein in the mechanism of labour. Moreover, several apolipoproteins such as apolipoprotein A-IV and APOE were found to change with labour, and these changes were also confirmed in maternal plasma. This study has identified significant protein changes in placental intervillous plasma with labour and has revealed several pathways related to human parturition.

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Section: Emergency Caesarean Sectionsupporting

confidence: 92%

Low abundance plasma proteins in labour

Wang¹,

Heesom²,

Phillips³

et al. 2012

Reproduction

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“…Two of the chemokines identified (CCL2: formally known as MCP-1, monocyte chemoattractant protein-1 and CXCL8: interleukin-8, IL-8) have been widely studied in the context of labour and are expressed in gestational tissues (myometrium, cervix, decidua) [18], [20], [25], [30], [31], [32], [33], [34]. Whilst the upregulation of CCL2 during labour was unsurprising as it coincides with elevated macrophage numbers in the decidua, high expression of neutrophil chemoattractant CXCL8 in tissues largely lacking neutrophil infiltration was unexpected.…”

Section: Discussionmentioning

confidence: 99%

Identification of Chemokines Associated with the Recruitment of Decidual Leukocytes in Human Labour: Potential Novel Targets for Preterm Labour

2013

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Current therapies for preterm labour (PTL) focus on arresting myometrial contractions but are largely ineffective, thus alternative therapeutic targets need to be identified. Leukocytes infiltrate the uterus around the time of labour, and are in particularly abundant in decidua (maternal-fetal interface). Moreover, decidual inflammation precedes labour in rat pregnancies and thus may contribute to initiation of labour. We hypothesized that chemokines mediate decidual leukocyte trafficking during preterm labour (PTL) and term labour (TL), thus representing potential targets for preventing PTL. Women were recruited into 4 groups: TL, term not in labour (TNL), idiopathic PTL and PTL with infection (PTLI). Choriodecidual RNA was subjected to a pathway-specific PCR array for chemokines. Differential expression of 12 candidate chemokines was validated by real time RT-PCR and Bioplex assay, with immunohistochemistry to confirm cellular origin. 25 chemokines were upregulated in choriodecidua from TL compared to TNL. A similar pattern was detected in PTL, however a distinct profile was observed in PTLI consistent with differences in leukocyte infiltration. Upregulation of CCL2, CCL4, CCL5, CXCL8 and CXCL10 mRNA and protein was confirmed in TL, with CCL8 upregulated in PTL. Significant correlations were detected between these chemokines and decidual leukocyte abundance previously assessed by immunohistochemical and image analysis. Chemokines were primarily expressed by decidual stromal cells. In addition, CXCL8 and CCL5 were significantly elevated in maternal plasma during labour, suggesting chemokines contribute to peripheral inflammatory events during labour. Differences in chemokine expression patterns between TL and idiopathic PTL may be attributable to suppression of chemokine expression by betamethasone administered to women in PTL; this was supported by in vitro evidence of chemokine downregulation by clinically relevant concentrations of the steroid. The current study provides compelling evidence that chemokines regulate decidual leukocyte recruitment during labour. The 6 chemokines identified represent potential novel therapeutic targets to block PTL.

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“…Chemokines such as MIP-1α, MCP-1, IL-8 and RANTES are increased during labor in amniotic fluid and this increase correlates with cervical dilation 33 and the number of leukocytes in reproductive tissues at term labor 35-37 . MIP-1α, IL-6 and MCP-1 are secreted by choriodecidual leukocytes 8, 31 and these signals may attract and activate additional lymphocytes and monocytes, among other leukocytes 34 .…”

Section: Discussionmentioning

confidence: 99%

Choriodecidual Cells From Term Human Pregnancies Show Distinctive Functional Properties Related to the Induction of Labor

Castillo-Castrejón

Meraz‐Cruz

Gomez‐Lopez

et al. 2013

American J Rep Immunol

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Problem Human parturition is associated with an intrauterine pro-inflammatory environment in the choriodecidua. Evidence that some mediators of this signaling cascade also elicit responses leading to labor prompted us to characterize the cellular sources of these mediators in the human choriodecidua. Method of study Leukocyte-enriched preparations from human choriodecidua (ChL) and intervillous placental blood leukocytes (PL) were maintained in culture. Secretions of inflammatory cytokines, chemokines and MMP-9 were documented. Leukocyte phenotype of ChL and PL was determined by flow cytometry using specific fluorochrome-conjugated antibodies. Results and Conclusions ChL showed a distinct pro-inflammatory secretion pattern of cytokines and chemokines when compared with PL, including higher amounts of TNF-α and IL-6, and decreased secretions of IL-4 and IL-1ra. ChL also secreted more MIP-1α and MCP-1 and MMP-9 than PL. No significant differences were found in leukocytes subsets between compartments. Based on our findings, we propose that ChL isolated from fetal membranes at term are functionally different from PL and may collaborate to modulate the microenvironment linked to induction and progression of human labor.

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Non-infected preterm parturition is related to increased concentrations of IL-6, IL-8 and MCP-1 in human cervix

Cited by 100 publications

References 60 publications

Low abundance plasma proteins in labour

Low abundance plasma proteins in labour

Identification of Chemokines Associated with the Recruitment of Decidual Leukocytes in Human Labour: Potential Novel Targets for Preterm Labour

Choriodecidual Cells From Term Human Pregnancies Show Distinctive Functional Properties Related to the Induction of Labor

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