Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.

Current therapies for preterm labour (PTL) focus on arresting myometrial contractions but are largely ineffective, thus alternative therapeutic targets need to be identified. Leukocytes infiltrate the uterus around the time of labour, and are in particularly abundant in decidua (maternal-fetal inter...

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Autores principales:	Sarah A Hamilton, Clare L Tower, Rebecca L Jones
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/76c0eee6ddbd42b79cae85fe70bed568
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spelling	oai:doaj.org-article:76c0eee6ddbd42b79cae85fe70bed5682021-11-18T07:56:23ZIdentification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.1932-620310.1371/journal.pone.0056946https://doaj.org/article/76c0eee6ddbd42b79cae85fe70bed5682013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23451115/?tool=EBIhttps://doaj.org/toc/1932-6203Current therapies for preterm labour (PTL) focus on arresting myometrial contractions but are largely ineffective, thus alternative therapeutic targets need to be identified. Leukocytes infiltrate the uterus around the time of labour, and are in particularly abundant in decidua (maternal-fetal interface). Moreover, decidual inflammation precedes labour in rat pregnancies and thus may contribute to initiation of labour. We hypothesized that chemokines mediate decidual leukocyte trafficking during preterm labour (PTL) and term labour (TL), thus representing potential targets for preventing PTL. Women were recruited into 4 groups: TL, term not in labour (TNL), idiopathic PTL and PTL with infection (PTLI). Choriodecidual RNA was subjected to a pathway-specific PCR array for chemokines. Differential expression of 12 candidate chemokines was validated by real time RT-PCR and Bioplex assay, with immunohistochemistry to confirm cellular origin. 25 chemokines were upregulated in choriodecidua from TL compared to TNL. A similar pattern was detected in PTL, however a distinct profile was observed in PTLI consistent with differences in leukocyte infiltration. Upregulation of CCL2, CCL4, CCL5, CXCL8 and CXCL10 mRNA and protein was confirmed in TL, with CCL8 upregulated in PTL. Significant correlations were detected between these chemokines and decidual leukocyte abundance previously assessed by immunohistochemical and image analysis. Chemokines were primarily expressed by decidual stromal cells. In addition, CXCL8 and CCL5 were significantly elevated in maternal plasma during labour, suggesting chemokines contribute to peripheral inflammatory events during labour. Differences in chemokine expression patterns between TL and idiopathic PTL may be attributable to suppression of chemokine expression by betamethasone administered to women in PTL; this was supported by in vitro evidence of chemokine downregulation by clinically relevant concentrations of the steroid. The current study provides compelling evidence that chemokines regulate decidual leukocyte recruitment during labour. The 6 chemokines identified represent potential novel therapeutic targets to block PTL.Sarah A HamiltonClare L TowerRebecca L JonesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56946 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah A Hamilton Clare L Tower Rebecca L Jones Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.
description	Current therapies for preterm labour (PTL) focus on arresting myometrial contractions but are largely ineffective, thus alternative therapeutic targets need to be identified. Leukocytes infiltrate the uterus around the time of labour, and are in particularly abundant in decidua (maternal-fetal interface). Moreover, decidual inflammation precedes labour in rat pregnancies and thus may contribute to initiation of labour. We hypothesized that chemokines mediate decidual leukocyte trafficking during preterm labour (PTL) and term labour (TL), thus representing potential targets for preventing PTL. Women were recruited into 4 groups: TL, term not in labour (TNL), idiopathic PTL and PTL with infection (PTLI). Choriodecidual RNA was subjected to a pathway-specific PCR array for chemokines. Differential expression of 12 candidate chemokines was validated by real time RT-PCR and Bioplex assay, with immunohistochemistry to confirm cellular origin. 25 chemokines were upregulated in choriodecidua from TL compared to TNL. A similar pattern was detected in PTL, however a distinct profile was observed in PTLI consistent with differences in leukocyte infiltration. Upregulation of CCL2, CCL4, CCL5, CXCL8 and CXCL10 mRNA and protein was confirmed in TL, with CCL8 upregulated in PTL. Significant correlations were detected between these chemokines and decidual leukocyte abundance previously assessed by immunohistochemical and image analysis. Chemokines were primarily expressed by decidual stromal cells. In addition, CXCL8 and CCL5 were significantly elevated in maternal plasma during labour, suggesting chemokines contribute to peripheral inflammatory events during labour. Differences in chemokine expression patterns between TL and idiopathic PTL may be attributable to suppression of chemokine expression by betamethasone administered to women in PTL; this was supported by in vitro evidence of chemokine downregulation by clinically relevant concentrations of the steroid. The current study provides compelling evidence that chemokines regulate decidual leukocyte recruitment during labour. The 6 chemokines identified represent potential novel therapeutic targets to block PTL.
format	article
author	Sarah A Hamilton Clare L Tower Rebecca L Jones
author_facet	Sarah A Hamilton Clare L Tower Rebecca L Jones
author_sort	Sarah A Hamilton
title	Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.
title_short	Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.
title_full	Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.
title_fullStr	Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.
title_full_unstemmed	Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.
title_sort	identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/76c0eee6ddbd42b79cae85fe70bed568
work_keys_str_mv	AT sarahahamilton identificationofchemokinesassociatedwiththerecruitmentofdecidualleukocytesinhumanlabourpotentialnoveltargetsforpretermlabour AT clareltower identificationofchemokinesassociatedwiththerecruitmentofdecidualleukocytesinhumanlabourpotentialnoveltargetsforpretermlabour AT rebeccaljones identificationofchemokinesassociatedwiththerecruitmentofdecidualleukocytesinhumanlabourpotentialnoveltargetsforpretermlabour
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Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.

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