Interleukin-8 Synthesis and the Onset of Labor

Osmers, R.; Bläser, Jörg; Kuhn, Walther; Tschesche, Harald

doi:10.1016/0029-7844(95)93704-4

Cited by 219 publications

(127 citation statements)

References 30 publications

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“…13 In parallel, upregulation of pro-inflammatory cytokines mRNA expression of Interleukin-1 b (IL-1b, IL-6, C-X-C motif ligand (CXCL) 8 and C-C motif ligand (CCL) 2 was observed in the myometrium of healthy labouring women. [14][15][16][17][18] Our recent data confirmed these findings and revealed a more extensive list of up-regulated cytokine and chemokine proteins (CXCL8, CXCL1, CCL2, CCL7, IL-9, IL-18, IL-1RN, tumor necrosis factor alpha (TNFa) and granulocyte colony-stimulating factor (G-CSF)) in healthy TL human myometrial tissue samples, while also detecting a higher number of macrophage and neutrophil infiltrate. 7,19 The trigger that elevates cytokines in the myometrium of healthy women during labour remains largely elusive.…”

Section: Introductionsupporting

confidence: 79%

“…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. 14,37,38 Recent reports of transcriptome data in spontaneous human labouring myometrial samples identified IL-6, CXCL1 and CXCL8 as highly expressed genes, with CXCL8 exhibiting the highest fold change in TL compared to term not-in-labour samples. 3,37 In line with our observations, Hua et al 31 showed that mechanical stretch augmented the expression of various chemokines in primary human myometrial myocytes including CCL2, CXCL8 and CXCL1.…”

Section: Discussionmentioning

confidence: 99%

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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: Introductionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

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

2014

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“…The chemokine IL-8 is largely responsible for the influx of leukocytes into uterine tissues, where it induces their degranulation and release of MMPs (Osmers et al 1995). MMPs are also produced by the cervix itself (Stygar et al 2002), as well as the placenta and fetal membranes (Xu et al 2002).…”

Section: Nf-kb Regulates Matrix Metalloproteinase Expressionmentioning

confidence: 99%

The role of nuclear factor kappa B in human labour

Lindström

Bennett²

2005

Reproduction

273

237

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Preterm birth remains the leading cause of perinatal mortality and morbidity, largely as a result of a poor understanding of the precise mechanisms controlling labour onset in humans. Inflammation has long been recognised as a key feature of both preterm and term labour, with an influx of inflammatory cells into the uterus and elevated levels of pro-inflammatory cytokines observed during parturition. Nuclear factor kappa B (NF-kB) is a transcription factor family classically associated with inflammation. Accumulating evidence points to a role for NF-kB in the physiology and pathophysiology of labour. NF-kB activity increases with labour onset and is central to multiple pro-labour pathways. Premature or aberrant activation of NF-kB may thus contribute to preterm labour. The current understanding of NF-kB in the context of human labour is discussed here.

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“…However, it remains unclear whether the inflammatory infiltration of the myometrium is a cause or consequence of labour. Human studies show that levels of IL-8 (Table 1) rise with established labour only (Osmers 1995, Elliott et al 2001, Kemp et al 2002a. In rodent pregnancies, it seems apparent that the inflammatory infiltration precedes the onset of labour (Mackler 1999, Shynlova et al 2012b), but various groups have depleted pregnant animals of neutrophils (Timmons 2006) or studied animals with no mast cells (Menzies et al 2011), without delaying labour onset.…”

Section: Myometrial Inflammationmentioning

confidence: 99%

Myometrial cytokines and their role in the onset of labour

Sivarajasingam

Imami

Johnson

2016

Journal of Endocrinology

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Human labour is an inflammatory event, physiologically driven by an interaction between hormonal and mechanical factors and pathologically associated with infection, bleeding and excessive uterine stretch. The initiation and communicators of inflammation is still not completely understood; however, a key role for cytokines has been implicated. We summarise the current understanding of the nature and role of cytokines, chemokines and hormones and their involvement in signalling within the myometrium particularly during labour.

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Interleukin-8 Synthesis and the Onset of Labor

Abstract: Interleukin-8 is critically involved in the process of parturition in humans. Interleukin-8 concentrations in the myometrium, decidua, and membranes correlated strongly with the observed MMP-8 and MMP-9 concentrations.

Cited by 219 publications

References 30 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

The role of nuclear factor kappa B in human labour

Myometrial cytokines and their role in the onset of labour

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