Human cathelicidin antimicrobial protein 18 (hCAP18/LL-37) is increased in foetal membranes and myometrium after spontaneous labour and delivery

Lim, Ratana; Barker, Gillian; Lappas, Martha

doi:10.1016/j.jri.2014.10.002

Cited by 17 publications

(11 citation statements)

References 67 publications

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“…These results coincide with previous studies demonstrating that choriodecidual leukocytes express CAMs [16,39,40], cytokines [8,41,42], chemokines [16,34], and their receptors [16,34,43], enzymes [35,44,45], antimicrobial peptides [46], markers of activation [17,39,[47][48][49], and even hormone receptors [50] before and during the process of labor. Together, these findings demonstrate that the choriodecidual leukocytes are a rich source of inflammatory mediators that can participate in the proinflammatory milieu that accompanies the process of labor.…”

Section: Resultssupporting

confidence: 92%

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

et al. 2018

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Prior to and during the process of human labor, maternal circulating leukocytes infiltrate the maternal-fetal interface (choriodecidua) and become activated resembling choriodecidual leukocytes. Since, there is no evidence comparing maternal circulating and choriodecidual leukocytes, herein, we characterized their transcriptome and explored the biological processes enriched in choriodecidual leukocytes. From women undergoing spontaneous term labor we isolated circulating and choriodecidual leukocytes, performed microarray analysis (n = 5) and qRT-PCR validation (n = 9) and interaction network analysis with up-regulated genes. We found 270 genes up-regulated and only 17 genes down-regulated in choriodecidual leukocytes compared to maternal circulating leukocytes. The most up-regulated genes were CCL18, GPNMB, SEPP1, FN1, RNASE1, SPP1, C1QC, and PLTP. The biological processes enriched in choriodecidual leukocytes were cell migration and regulation of immune response, chemotaxis, and humoral immune responses. Our results show striking differences between the transcriptome of choriodecidual and maternal circulating leukocytes. Choriodecidual leukocytes are enriched in immune mediators implicated in the spontaneous process of labor at term.

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Section: Resultssupporting

confidence: 92%

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

et al. 2018

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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: 87%

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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“…These findings are in line with those of Lim et al . who found an increase in LL-37 protein levels in human myometrium from term women in labour compared to term women undergoing a pre-labour caesarean section 42 . They found LL-37 localised to myometrial muscle fibres in both labouring and pre-labouring samples, and in labouring samples LL-37 was also found in leukocytes 42 .…”

Section: Discussionmentioning

confidence: 95%

“…who found an increase in LL-37 protein levels in human myometrium from term women in labour compared to term women undergoing a pre-labour caesarean section 42 . They found LL-37 localised to myometrial muscle fibres in both labouring and pre-labouring samples, and in labouring samples LL-37 was also found in leukocytes 42 . LL-37 is known to be predominantly produced by neutrophils and epithelial cells 3 and as there is an influx of neutrophils in term and pre-term labouring myometrium 17,43 , we hypothesise that the LL-37 increase is at least in part due to this infiltration 20,21 .…”

Section: Discussionmentioning

confidence: 95%

Cathelicidins and the Onset of Labour

Boeckel

Hrabálková

Baker

et al. 2019

Sci Rep

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Preterm birth, defined as delivery before 37 weeks of gestation, is the leading cause of neonatal mortality and morbidity. Infection and inflammation are frequent antecedents of spontaneous preterm birth. Cathelicidin, an antimicrobial host defence peptide, is induced by infection and inflammation and although expressed in the reproductive tract and fetal tissues, its role in the pathogenesis of spontaneous preterm birth is unknown. Here we demonstrate that cathelicidin expression is increased at RNA and protein level in the mouse uterus in a model of inflammation-induced labour, where ultrasound guided intrauterine injection of lipopolysaccharide (LPS) at E17 stimulates preterm delivery within 24 hours. Cathelicidin-deficient ( Camp −/− ) mice are less susceptible to preterm delivery than wild type mice following intrauterine injection of 1 μg of LPS, and this is accompanied by a decrease in circulating IL-6, an inflammatory mediator implicated in the onset of labour. We also show that the proportion of cathelicidin expressing cells in the myometrium is higher in samples obtained from women in labour at term than pre-labour. Together, these data suggest that cathelicidin has roles in mediating pro-inflammatory responses in a murine model of inflammation-induced labour, and in human term labour.

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Human cathelicidin antimicrobial protein 18 (hCAP18/LL-37) is increased in foetal membranes and myometrium after spontaneous labour and delivery

Cited by 17 publications

References 67 publications

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

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

Cathelicidins and the Onset of Labour

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