Leukocyte density and pro-inflammatory cytokine expression in human fetal membranes, decidua, cervix and myometrium before and during labour at term

Osman, Inass; Young, Anne; Ledingham, Marie Anne; Thomson, Andrew J.; Jordan, Fiona; Greer, Ian A.; Norman, Jane E.

doi:10.1093/molehr/gag001

Cited by 627 publications

(569 citation statements)

References 18 publications

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“…IL-6 promotes synchronous myometrial contraction via PG synthesis and expression of oxytocin and its receptor. [32][33][34][35] Furthermore, IL-6 2/2 mice showed impaired leukocyte accumulation, suggesting that IL-6 also plays a role in leukocyte recruitment. 36 Two CXC family chemokines (CXCL1 and CXCL8) are well known for their strong chemoattractant activity on neutrophils, and their expression in human myometrium during spontaneous labour was reported and confirmed by many research groups.…”

Section: Discussionmentioning

confidence: 98%

Stretch-induced human myometrial cytokines enhance immune cell recruitment via endothelial activation

2014

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Spontaneous term labour is associated with amplified inflammatory events in the myometrium including cytokine production and leukocyte infiltration; however, potential mechanisms regulating such events are not fully understood. We hypothesized that mechanical stretch of the uterine wall by the growing fetus facilitates peripheral leukocyte extravasation into the term myometrium through the release of various cytokines by uterine myocytes. Human myometrial cells (hTERT-HM) were subjected to static mechanical stretch; stretch-conditioned media was collected and analysed using 48-plex Luminex assay and ELISA. Effect of stretch-conditioned media on cell adhesion molecule expression of human uterine microvascular endothelial cells (UtMVEC-Myo) was detected by quantitative polymerase chain reaction (qPCR) and flow cytometry; functional assays testing leukocyte-endothelial interactions: adhesion of leukocytes to endothelial cells and transendothelial migration of calcein-labelled primary human neutrophils as well as migration of THP-1 monocytic cells were assessed by fluorometry. The current in vitro study demonstrated that mechanical stretch (i) directly induces secretion of multiple cytokines and chemokines by hTERT-HM cells (IL-6, CXCL8, CXCL1, migration inhibitory factor (MIF), VEGF, G-CSF, IL-12p70, bFGF and platelet-derived growth factor subunit B (PDGF-bb), P,0.05); stretch-induced cytokines (ii) enhance leukocyte adhesion to the endothelium of the surrounding uterine microvasculature by (iii) inducing the expression of endothelial cell adhesion molecules and (iv) directing the transendothelial migration of peripheral leukocytes. (vi) Chemokine-neutralizing antibodies and broad-spectrum chemokine inhibitor block leukocyte migration. Our data provide a proof of mechanical regulation for leukocyte recruitment from the uterine blood vessels to the myometrium, suggesting a putative mechanism for the leukocyte infiltrate into the uterus during labour and postpartum involution.

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Section: Discussionmentioning

confidence: 98%

Stretch-induced human myometrial cytokines enhance immune cell recruitment via endothelial activation

2014

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“…At its most basic level, this concept is supported by the demonstration that leukocytes, (largely neutrophils and macrophages, and also T cells) invade the myometrium, cervix and fetal membranes at or immediately after the onset of labour (Osman et al, 2003, Thomson et al, 1999, attracted by increased tissue expression of chemokines and cell adhesion molecules (Ledingham et al, 2001, Winkler et al, 1998. In parallel, leukocytes circulating in the peripheral blood increase their expression of cell adhesion molecule ligands such as CD11a and CD11b (Yuan et al, 2009), facilitating leukocyte emigration into the myometrium and cervix.…”

Section: Labour As An Inflammatory Eventmentioning

confidence: 99%

“…The increased expression of cytokines in the myometrium and cervix in labour (Osman et al, 2003) arises in part from the invading leukocytes (Young et al, 2002) with recent evidence suggesting that increased capacity of leukocytes in labour to express cytokines is initiated in the peripheral circulation (Yuan et al, 2009). These pro-inflammatory cytokines have a multitude of effects on the reproductive tissues, including stimulatory effects on myometrial contractility via a number of different mechanisms, discussed below.…”

Section: Labour As An Inflammatory Eventmentioning

confidence: 99%

“…Leukocyte invasion and the increase in protein concentrations of IL-8, IL-6 and granulocyte-CSF (G-CSF) observed in the human cervical connective tissue at term and subsequently in labour are likely to be crucial to the process of cervical remodelling to facilitate opening during parturition (Osman et al, 2003, Sennstrom et al, 2000. Functionally, IL-8 may stimulate the release of degradative enzymes from neutrophils.…”

Section: The Cervixmentioning

confidence: 99%

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Endocrine immune interactions in human parturition

Golightly

Jabbour

Norman

2011

Molecular and Cellular Endocrinology

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Human parturition is an inflammatory event, modulated and influenced by a host of other environmental and physiological processes, including the endocrine hormones.Complex bidirectional communication occurs between the two systems to bring about some of the changes that are seen in labour, an event that is not yet fully understood.Preterm birth is a major problem in obstetrics and neonatology, with dysfunctional labour or prolonged pregnancy also making increasingly significant contributions to maternal morbidity. With better understanding of normal and abnormal parturition we may be able to develop novel ways of treating these complications of pregnancy and reduce maternal and neonatal morbidity and mortality. This review discusses the crucial role that endocrine-immune interaction plays in the process of labour and in the processes of abnormal and preterm labour. We propose that amongst these complex interactions it is the immune system that is the driving force behind human parturition. Keywords Parturition Endocrine InflammationImmune

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“…The myometrial receptor and hormonal changes shift the uterus from a quiescent to an active rhythmically contractile state. Concomitant with these changes, inflammatory events occur in the cervix, such as increased production of proinflammatory cytokines such as interleukin-1b (IL-1b), IL-6, IL-8 (14-16), and PGE 2 (15), which trigger cervical ripening.…”

Section: Introductionmentioning

confidence: 99%

Maternal serum progesterone, estradiol and estriol levels in successful dinoprostone-induced labor

Konopka¹,

Morais²,

Naidon³

et al. 2013

Braz. J. Med. Biol. Res.

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Hormone-mediated quiescence involves the maintenance of a decreased inflammatory responsiveness. However, no study has investigated whether labor induction with prostanoids is associated with changes in the levels of maternal serum hormones. The objective of this study was to determine whether labor induction with dinoprostone is associated with changes in maternal serum progesterone, estradiol, and estriol levels. Blood samples were obtained from 81 pregnant women at term. Sixteen patients had vaginal birth after spontaneous labor, 12 required cesarean section after spontaneous labor and 16 underwent elective cesarean. Thirty-seven patients had labor induction with dinoprostone. Eligible patients received a vaginal insert of dinoprostone (10 mg) and were followed until delivery. Serum progesterone (P4), estradiol (E2) and estriol (E3) levels and changes in P4/E2, P4/E3 and E3/E2 ratios were monitored from admission to immediately before birth, and the association of these measures with the resulting clinical classification outcome (route of delivery and induction responsiveness) was assessed. Progesterone levels decreased from admission to birth in patients who underwent successful labor induction with dinoprostone [vaginal and cesarean birth after induced labor: 23% (P , 0.001) and 18% (P , 0.025) decrease, respectively], but not in those whose induction failed (6.4% decrease, P . 0.05). Estriol and estradiol levels, P4/E2, P4/E3 and E3/E2 ratios did not differ between groups. Successful dinoprostone-induced labor was associated with reduced maternal progesterone levels from induction to birth. While a causal relationship between progesterone decrease and effective dinoprostone-induced labor cannot be established, it is tempting to propose that dinoprostone may contribute to progesterone withdrawal and favor labor induction in humans.

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Leukocyte density and pro-inflammatory cytokine expression in human fetal membranes, decidua, cervix and myometrium before and during labour at term

Cited by 627 publications

References 18 publications

Stretch-induced human myometrial cytokines enhance immune cell recruitment via endothelial activation

Stretch-induced human myometrial cytokines enhance immune cell recruitment via endothelial activation

Endocrine immune interactions in human parturition

Maternal serum progesterone, estradiol and estriol levels in successful dinoprostone-induced labor

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