Inflammatory processes in preterm and term parturition

Christiaens, Inge; Zaragoza, Dean B.; Guilbert, Larry J.; Robertson, Sarah A.; Mitchell, Bryan F.; Olson, David M.

doi:10.1016/j.jri.2008.04.002

Cited by 442 publications

(367 citation statements)

References 67 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%

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%

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

2014

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“…Most other studies include women who had already miscarried. [66][67][68] In contrast to what previous investigators have carried out, where experiments were done on cultured peripheral blood mononuclear cells, 69,70 fluorescent antibody-labeled whole blood was analyzed by flow cytometry in this case. In view of the patient groups that were recruited (pregnant women who were experiencing vaginal bleeding in the first trimester), we aimed to sample smaller volumes of blood (1 mL) for the entire experiment (100 L/cytokine or receptor), compared with a minimum of 50 mL in the peripheral blood mononuclear cell culture experiments.…”

Section: Wwwajogorgmentioning

confidence: 99%

Pro- and antiinflammatory cytokines in threatened miscarriages

Calleja‐Agius

Muttukrishna

Pizzey

et al. 2011

American Journal of Obstetrics and Gynecology

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OBJECTIVE:The purpose of this study was to evaluate circulating and intracellular levels of Th1 and Th2 cytokines in women with threatened miscarriage (TM) and subsequent outcome.STUDY DESIGN: Plasma levels of tumor necrosis factor (TNF)-receptors 1 and 2, TNF␣, interferon gamma (IFN␥), and interleukins (IL) -6 and -10 were measured by flow cytometric bead assays in 80 women with TM: 53 women with normal outcome and 27 women who miscarried. Fluorescent antibody labeling was also performed on whole blood in a subgroup of 27 women of TM: 16 women with normal outcome and 11 women who miscarried. RESULTS:Monocyte expression of TNF␣ and circulating levels of TNF␣, IFN␥, IL-10, IL-6, and TNF-R1 were significantly lower, whereas circulating levels of TNF␣/IL-10, IFN␥/IL-10, and TNF␣/IL-6 ratios were significantly higher, in women with TM who subsequently miscarried, compared with the women with normal outcome.CONCLUSION: An increased Th1 type of immune response, which was similar to that observed in preterm delivery, was found in TM cases that were complicated by a subsequent miscarriage.

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“…Interestingly, in fibroblasts bradykinin-induced p38 phosphorylation stimulates the production of two pro-inflammatory cytokines, interleukin (IL) 6 and IL8, both of which are strongly correlated to initiation of labour (Christiaens et al, 2008). It is therefore conceivable that bradykinin may play a similar role in the myometrium during infections to help initiate labour.…”

Section: Discussionmentioning

confidence: 99%

Bradykinin-activated contractile signalling pathways in human myometrial cells are differentially regulated by arrestin proteins

Willets

Brighton

Windell

et al. 2015

Molecular and Cellular Endocrinology

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Bradykinin is associated with infections and inflammation, which given the strong correlation between uterine infection and preterm labour may imply that it could play a role in this process. Therefore, we investigated bradykinin signalling, and the roles that arrestin proteins play in their regulation in human myometrial cells. Bradykinin induced rapid, transient intracellular Ca 2+ increases that were inhibited following B 2 receptor (B 2 R) antagonism.

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Inflammatory processes in preterm and term parturition

Cited by 442 publications

References 67 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

Pro- and antiinflammatory cytokines in threatened miscarriages

Bradykinin-activated contractile signalling pathways in human myometrial cells are differentially regulated by arrestin proteins

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