Placental Chemokine Receptor D6 Is Functionally Impaired in Pre-Eclampsia.
Pre-eclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality worldwide. It is defined by new onset of hypertension and proteinuria after the 20th week of gestation and characterized by systemic exaggerated inflammatory response. D6 is a chemokines scavenger receptor that bin...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5079655?pdf=render |
| _version_ | 1811322529486209024 |
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| author | Chiara Tersigni Fiorella Di Nicuolo Giuseppe Maulucci Alessandro Rolfo Domenica Giuffrida Manuela Veglia Marco De Spirito Giovanni Scambia Tullia Todros Nicoletta Di Simone |
| author_facet | Chiara Tersigni Fiorella Di Nicuolo Giuseppe Maulucci Alessandro Rolfo Domenica Giuffrida Manuela Veglia Marco De Spirito Giovanni Scambia Tullia Todros Nicoletta Di Simone |
| author_sort | Chiara Tersigni |
| collection | DOAJ |
| description | Pre-eclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality worldwide. It is defined by new onset of hypertension and proteinuria after the 20th week of gestation and characterized by systemic exaggerated inflammatory response. D6 is a chemokines scavenger receptor that binds with high affinity CC chemokines, internalizes and targets the ligands for degradation. It is expressed in trophoblast-derived tissues and prevents excessive placenta leukocyte infiltration.The aim of this study was to investigate the expression and function of D6 in human placentae from pre-eclamptic and healthy pregnant women.Plasma levels of D6-binding CC chemokines (CCL-2, CCL-3, CCL-4, CCL-7, CCL-11) and pro-inflammatory cytokines (IL-6, TNF-α, CRP) were analyzed in 37 healthy pregnant women and 38 patients with PE by multiplex bead assay. Higher circulating levels of CCL7, CCL11, IL-6, (p<0.0001) and CRP (p<0.05) were observed in PE women compared to controls. Levels of circulating CCL4 were decreased in PE (p<0.001), while no significant differences of CCL2, CCL3 or TNF-α levels were detected. Immunofluorescent staining of placental sections showed higher expression of D6 receptor in the PE syncytiotrophoblast. Confocal and Western blot (WB) analyses revealed a prevalent distribution of D6 in trophoblast cells membranes in PE. Increased activation of D6 intracellular pathway was observed by Western blot analyses of p-LIMK and p-cofilin in trophoblast cell lysates. D6 functional assays showed reduced scavenging of CCL2 in PE cells compared to controls. Since actin filaments spatial assembling is essential for D6 intracellular trafficking and scavenging activity, we investigated by confocal microscopy trophoblast cytoskeleton organization and we observed a dramatic disarrangement in PE compared to controls.our results suggest membrane distribution of D6 receptor on trophoblast cell membranes in PE, together with reduced functionality, probably due to cytoskeleton impairment. |
| first_indexed | 2024-04-13T13:36:39Z |
| format | Article |
| id | doaj.art-322d6e7ac18c430c8afa6599f22f4c22 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T13:36:39Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-322d6e7ac18c430c8afa6599f22f4c222022-12-22T02:44:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011110e016474710.1371/journal.pone.0164747Placental Chemokine Receptor D6 Is Functionally Impaired in Pre-Eclampsia.Chiara TersigniFiorella Di NicuoloGiuseppe MaulucciAlessandro RolfoDomenica GiuffridaManuela VegliaMarco De SpiritoGiovanni ScambiaTullia TodrosNicoletta Di SimonePre-eclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality worldwide. It is defined by new onset of hypertension and proteinuria after the 20th week of gestation and characterized by systemic exaggerated inflammatory response. D6 is a chemokines scavenger receptor that binds with high affinity CC chemokines, internalizes and targets the ligands for degradation. It is expressed in trophoblast-derived tissues and prevents excessive placenta leukocyte infiltration.The aim of this study was to investigate the expression and function of D6 in human placentae from pre-eclamptic and healthy pregnant women.Plasma levels of D6-binding CC chemokines (CCL-2, CCL-3, CCL-4, CCL-7, CCL-11) and pro-inflammatory cytokines (IL-6, TNF-α, CRP) were analyzed in 37 healthy pregnant women and 38 patients with PE by multiplex bead assay. Higher circulating levels of CCL7, CCL11, IL-6, (p<0.0001) and CRP (p<0.05) were observed in PE women compared to controls. Levels of circulating CCL4 were decreased in PE (p<0.001), while no significant differences of CCL2, CCL3 or TNF-α levels were detected. Immunofluorescent staining of placental sections showed higher expression of D6 receptor in the PE syncytiotrophoblast. Confocal and Western blot (WB) analyses revealed a prevalent distribution of D6 in trophoblast cells membranes in PE. Increased activation of D6 intracellular pathway was observed by Western blot analyses of p-LIMK and p-cofilin in trophoblast cell lysates. D6 functional assays showed reduced scavenging of CCL2 in PE cells compared to controls. Since actin filaments spatial assembling is essential for D6 intracellular trafficking and scavenging activity, we investigated by confocal microscopy trophoblast cytoskeleton organization and we observed a dramatic disarrangement in PE compared to controls.our results suggest membrane distribution of D6 receptor on trophoblast cell membranes in PE, together with reduced functionality, probably due to cytoskeleton impairment.http://europepmc.org/articles/PMC5079655?pdf=render |
| spellingShingle | Chiara Tersigni Fiorella Di Nicuolo Giuseppe Maulucci Alessandro Rolfo Domenica Giuffrida Manuela Veglia Marco De Spirito Giovanni Scambia Tullia Todros Nicoletta Di Simone Placental Chemokine Receptor D6 Is Functionally Impaired in Pre-Eclampsia. PLoS ONE |
| title | Placental Chemokine Receptor D6 Is Functionally Impaired in Pre-Eclampsia. |
| title_full | Placental Chemokine Receptor D6 Is Functionally Impaired in Pre-Eclampsia. |
| title_fullStr | Placental Chemokine Receptor D6 Is Functionally Impaired in Pre-Eclampsia. |
| title_full_unstemmed | Placental Chemokine Receptor D6 Is Functionally Impaired in Pre-Eclampsia. |
| title_short | Placental Chemokine Receptor D6 Is Functionally Impaired in Pre-Eclampsia. |
| title_sort | placental chemokine receptor d6 is functionally impaired in pre eclampsia |
| url | http://europepmc.org/articles/PMC5079655?pdf=render |
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