Interleukin 8 Expression in Human Myometrium: Changes in Relation to Labor Onset and with Gestational Age

C.L., ELLIOTT; D.M., SLATER; Dennes, William; P.R., BENNETT; Poston, L.

doi:10.1111/j.8755-8920.2000.430505.x

Cited by 47 publications

(5 citation statements)

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“…7, 17, 18, 23, 24, 25, 41, 42, 45, 46, 47, 48, 49 Increased IL-8 mRNA was also seen in term labor tissues and in vitro labor experiments. 18, 19, 28, 29, 30, 31, 32, 34, 35, 37, 42, 45, 47, 48, 49, 50, 51, 52, 53, 54, 55 There were some contradictory findings to the conclusions above. Keelan et al 1999 found that there was no change in IL-8 protein in the placenta 6 and Kelly et al 1992 found no change in IL-8 protein levels in choriodecidua after labor onset.…”

Section: Discussionmentioning

confidence: 84%

Gestational tissue inflammatory biomarkers at term labor: A systematic review of literature

Hadley

Richardson

Torloni

et al. 2017

American J Rep Immunol

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Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory biomarkers linked to labor, a comprehensive profile of them in each of the uterine compartments is not available to better understand their mechanistic contributions to labor. This systematic review investigated the pro- and anti-inflammatory biomarkers reported in intra-uterine tissues (amnion, chorion, decidua, placenta, and myometrium) at term labor. We conducted a systematic review of studies on pro- and anti-inflammatory biomarkers (mRNA and/or protein) reported in feto-maternal tissues during normal human term labor, published in English (1980-2016), in 3 electronic data bases. From a total of 3712 citations, 172 were included for final review. Each tissue expresses a unique set of biomarkers at the time of term labor, but there is significant overlap between tissues. All tissues had IL-6, IL-8, IL-1β, COX-2, PGE-2, TNF-α, and hCAP18 in common at term labor. Common and unique inflammatory biomarkers are expressed in various feto-maternal compartments at term labor. Increase in pro-inflammatory markers in all gestational tissue signifies their harmonious functional role in promoting labor. Anti-inflammatory markers at term labor are hardly reported.

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Section: Discussionmentioning

confidence: 84%

Gestational tissue inflammatory biomarkers at term labor: A systematic review of literature

Hadley

Richardson

Torloni

et al. 2017

American J Rep Immunol

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“…These outputs were chosen because both COX-2 and CXCL8 are demonstrated to increase in human myometrium with labour [2,16]. Expression of COX-2 was first examined comparing upper segment versus lower segment cells, In non-treated cells expression of COX-2 was significantly higher in lower segment cells compared to upper segment cells ( P < 0.0001) (Figure 4A).…”

Section: Resultsmentioning

confidence: 99%

Development and validation of primary human myometrial cell culture models to study pregnancy and labour

Mosher

Rainey

Bolstad

et al. 2013

BMC Pregnancy Childbirth

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Background The development of the in vitro cell culture model has greatly facilitated the ability to study gene expression and regulation within human tissues. Within the human uterus, the upper (fundal) segment and the lower segment may provide distinct functions throughout pregnancy and during labour. We have established primary cultured human myometrial cells, isolated from both upper and lower segment regions of the pregnant human uterus, and validated them for the purpose of studying human pregnancy and labour. The specific objectives of this study were to monitor the viability and characterize the expression profile using selected cellular, contractile and pregnancy associated markers in the primary cultured human myometrial cells. Labour has been described as an inflammatory process; therefore, the ability of these cells to respond to an inflammatory stimulus was also investigated. Methods Myometrial cells isolated from paired upper segment (US) and lower segment (LS) biopsies, obtained from women undergoing Caesarean section deliveries at term prior to the onset of labour, were used to identify expression of; α smooth muscle actin, calponin, caldesmon, connexin 43, cyclo-oxygenase-2 (COX-2), oxytocin receptor, tropomyosin and vimentin, by RT-PCR and/or immunocytochemistry. Interleukin (IL)-1β was used to treat cells, subsequently expression of COX-2 mRNA and release of interleukin-8 (CXCL8), were measured. ANOVA followed by Bonferroni’s multiple comparisons test was performed. Results We demonstrate that US and LS human myometrial cells stably express all markers examined to at least passage ten (p10). Connexin 43, COX-2 and vimentin mRNA expression were significantly higher in LS cells compared to US cells. Both cell populations respond to IL-1β, demonstrated by a robust release of CXCL8 and increased expression of COX-2 mRNA from passage one (p1) through to p10. Conclusions Isolated primary myometrial cells maintain expression of smooth muscle and pregnancy-associated markers and retain their ability to respond to an inflammatory stimulus. These distinct myometrial cell models will provide a useful tool to investigate mechanisms underlying the process of human labour and the concept of functional regionalization of the pregnant uterus.

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“…The increase in leukocyte density, in part, leads to increased cytokine expression in the myometrium and cervix [ 41 , 50 ]. These cytokines attract yet more leukocytes [ 51 ], but also have a pronounced effect on the reproductive tissues, including remodelling of the cervix [ 52 ] and stimulating myometrial contraction through prostaglandin synthesis and via direct TLR-4 mediated effects [ 53 – 59 ]. Prostaglandins mediate inflammation and some have a direct contractile effect on myometrial myocytes [ 60 – 63 ].…”

Section: Discussionmentioning

confidence: 99%

Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women

et al. 2016

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An incomplete understanding of the molecular mechanisms that initiate normal human labour at term seriously hampers the development of effective ways to predict, prevent and treat disorders such as preterm labour. Appropriate analysis of large microarray experiments that compare gene expression in non-labouring and labouring gestational tissues is necessary to help bridge these gaps in our knowledge. In this work, gene expression in 48 (22 labouring, 26 non-labouring) lower-segment myometrial samples collected at Caesarean section were analysed using Illumina HT-12 v4.0 BeadChips. Normalised data were compared between labouring and non-labouring groups using traditional statistical methods and a novel network graph approach. We sought technical validation with quantitative real-time PCR, and biological replication through inverse variance-weighted meta-analysis with published microarray data. We have extended the list of genes suggested to be associated with labour: Compared to non-labouring samples, labouring samples showed apparent higher expression at 960 probes (949 genes) and apparent lower expression at 801 probes (789 genes) (absolute fold change ≥1.2, rank product percentage of false positive value (RP-PFP) <0.05). Although half of the women in the labouring group had received pharmaceutical treatment to induce or augment labour, sensitivity analysis suggested that this did not confound our results. In agreement with previous studies, functional analysis suggested that labour was characterised by an increase in the expression of inflammatory genes and network analysis suggested a strong neutrophil signature. Our analysis also suggested that labour is characterised by a decrease in the expression of muscle-specific processes, which has not been explicitly discussed previously. We validated these findings through the first formal meta-analysis of raw data from previous experiments and we hypothesise that this represents a change in the composition of myometrial tissue at labour. Further work will be necessary to reveal whether these results are solely due to leukocyte infiltration into the myometrium as a mechanism initiating labour, or in addition whether they also represent gene changes in the myocytes themselves. We have made all our data available at www.ebi.ac.uk/arrayexpress/ (accession number E-MTAB-3136) to facilitate progression of this work.

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Interleukin 8 Expression in Human Myometrium: Changes in Relation to Labor Onset and with Gestational Age

Abstract: The increased expression of IL-8 in laboring myometria at term supports the hypothesis that up-regulation of IL-8 has a role in the initiation of labor in association with an influx of neutrophils and the release of their collagenolytic enzymes into uterine tissues.

Cited by 47 publications

References 0 publications

Gestational tissue inflammatory biomarkers at term labor: A systematic review of literature

Gestational tissue inflammatory biomarkers at term labor: A systematic review of literature

Development and validation of primary human myometrial cell culture models to study pregnancy and labour

Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women

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