Cytokines, Prostaglandins and Parturition—A Review

Keelan, Jeffrey A.; Blumenstein, Marion; Helliwell, Rachel J. A.; Sato, Timothy A.; Marvin, Keith W.; Mitchell, Murray D.

doi:10.1053/plac.2002.0948

Cited by 536 publications

(416 citation statements)

References 163 publications

(29 reference statements)

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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: 99%

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: 99%

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

2014

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“…Similarly, proinflammatory cytokines have also been found in serum/plasma collected from healthy pregnant sows [59] as well as pregnant women [4,24,57]. The proinflammatory cytokines have been proposed to play a physiological role at parturition by being involved in the regulation of the parturition as such [13,29]. Also, cytokines appear to be an important component of a paracrine/autocrine communication network in the mammary gland at different stages of pregnancy and parturition [25,44].…”

Section: Discussionmentioning

confidence: 99%

Morphometric analysis of proinflammatory cytokines in mammary glands of sows suggests an association between clinical mastitis and local production of IL-1beta, IL-6 and TNF-alpha

et al. 2007

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-Twelve healthy primiparous sows received intramammary inoculation with Escherichia coli (serotype O127) during the 24-h period preceding parturition. Mammary gland biopsy samples were taken immediately before inoculation (0 h) and from the inoculated and the contralateral noninoculated glands 24 h after inoculation. The analyses of interleukin-1 beta (IL-1β), IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) by immunohistochemistry revealed that the production of these proinflammatory cytokines significantly increased in the inoculated mammary glands of sows that developed clinical signs of mastitis (affected group, n = 4) 24 h after inoculation. This was also true for IL-8 in the inoculated mammary glands of sows that did not develop clinical signs of mastitis (nonaffected group, n = 8). Sows that developed clinical signs of mastitis displayed significantly lower constitutive production of IL-1β than did sows that remained clinically healthy. The data indicate that the development of clinical symptoms of coliform mastitis in the sow is associated with a locally increased proinflammatory cytokine production in response to intramammary E. coli infection.cytokine / immunohistochemistry / mastitis / pig / E. coli

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“…However, the processes involved are not fully understood, especially the triggers/activators of labour. Local pro-inflammatory cytokine and chemokines have been implicated in the pathophysiology of human labour since the 1980s; with more recent data strongly linking increased intrauterine cytokine and chemokine production with both term (TL) and preterm labour (PTL) (Keelan et al 2003).…”

Section: Introductionmentioning

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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Cytokines, Prostaglandins and Parturition—A Review

Cited by 536 publications

References 163 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

Morphometric analysis of proinflammatory cytokines in mammary glands of sows suggests an association between clinical mastitis and local production of IL-1beta, IL-6 and TNF-alpha

Myometrial cytokines and their role in the onset of labour

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