Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm Infants
Background: Preterm infants exposed to chorioamnionitis and with a fetal inflammatory response are at risk for neonatal morbidity and adverse outcome. Alarmins S100A8, S100A9, and S100A12 are expressed by myeloid cells and have been associated with inflammatory activation and monocyte modulation.Aim...
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01194/full |
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| author | Veronika Golubinskaya Henri Puttonen Ing-Marie Fyhr Halfdan Rydbeck Ann Hellström Bo Jacobsson Bo Jacobsson Bo Jacobsson Holger Nilsson Carina Mallard Karin Sävman Karin Sävman |
| author_facet | Veronika Golubinskaya Henri Puttonen Ing-Marie Fyhr Halfdan Rydbeck Ann Hellström Bo Jacobsson Bo Jacobsson Bo Jacobsson Holger Nilsson Carina Mallard Karin Sävman Karin Sävman |
| author_sort | Veronika Golubinskaya |
| collection | DOAJ |
| description | Background: Preterm infants exposed to chorioamnionitis and with a fetal inflammatory response are at risk for neonatal morbidity and adverse outcome. Alarmins S100A8, S100A9, and S100A12 are expressed by myeloid cells and have been associated with inflammatory activation and monocyte modulation.Aim: To study S100A alarmin expression in cord blood monocytes from term healthy and preterm infants and relate results to clinical findings, inflammatory biomarkers and alarmin protein levels, as well as pathways identified by differentially regulated monocyte genes.Methods: Cord blood CD14+ monocytes were isolated from healthy term (n = 10) and preterm infants (<30 weeks gestational age, n = 33) by MACS technology. Monocyte RNA was sequenced and gene expression was analyzed by Principal Component Analysis and hierarchical clustering. Pathways were identified by Ingenuity Pathway Analysis. Inflammatory proteins were measured by Multiplex ELISA, and plasma S100A proteins by mass spectrometry. Histological chorioamnionitis (HCA) and fetal inflammatory response syndrome (FIRS) were diagnosed by placenta histological examination.Results: S100A8, S100A9, and S100A12 gene expression was significantly increased and with a wider range in preterm vs. term infants. High S100A8 and S100A9 gene expression (n = 17) within the preterm group was strongly associated with spontaneous onset of delivery, HCA, FIRS and elevated inflammatory proteins in cord blood, while low expression (n = 16) was associated with impaired fetal growth and physician-initiated delivery. S100A8 and S100A9 protein levels were significantly lower in preterm vs. term infants, but within the preterm group high S100A gene expression, spontaneous onset of labor, HCA and FIRS were associated with elevated protein levels. One thousand nine hundred genes were differentially expressed in preterm infants with high vs. low S100A alarmin expression. Analysis of 124 genes differentially expressed in S100A high as well as FIRS and HCA groups identified 18 common pathways and S100A alarmins represented major hubs in network analyses.Conclusion: High expression of S100A alarmins in cord blood monocytes identifies a distinct clinical risk group of preterm infants exposed to chorioamnionitis and with a fetal inflammatory response. Gene and pathway analyses suggest that high S100A alarmin expression also affects monocyte function. The connection with monocyte phenotype and inflammation-stimulated S100A expression in other cell types (e.g., neutrophils) warrants further investigation. |
| first_indexed | 2024-12-11T00:16:24Z |
| format | Article |
| id | doaj.art-969c89053f4d488596ada2f2f2411d90 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T00:16:24Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj.art-969c89053f4d488596ada2f2f2411d902022-12-22T01:27:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-06-011110.3389/fimmu.2020.01194516173Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm InfantsVeronika Golubinskaya0Henri Puttonen1Ing-Marie Fyhr2Halfdan Rydbeck3Ann Hellström4Bo Jacobsson5Bo Jacobsson6Bo Jacobsson7Holger Nilsson8Carina Mallard9Karin Sävman10Karin Sävman11Department of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, SwedenDepartment of Pathology, Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Pathology, Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, SwedenDepartment of Clinical Neuroscience, Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, SwedenDepartment of Obstetrics and Gynecology, Institute of Clinical Science, University of Gothenburg, Sahlgrenska Academy, Gothenburg, SwedenDepartment of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Genetics and Bioinformatics, Domain of Health Data and Digitalization, Institute of Public Health, Oslo, NorwayDepartment of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, SwedenDepartment of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, SwedenDepartment of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska Academy, Gothenburg, SwedenDepartment of Neonatology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, SwedenBackground: Preterm infants exposed to chorioamnionitis and with a fetal inflammatory response are at risk for neonatal morbidity and adverse outcome. Alarmins S100A8, S100A9, and S100A12 are expressed by myeloid cells and have been associated with inflammatory activation and monocyte modulation.Aim: To study S100A alarmin expression in cord blood monocytes from term healthy and preterm infants and relate results to clinical findings, inflammatory biomarkers and alarmin protein levels, as well as pathways identified by differentially regulated monocyte genes.Methods: Cord blood CD14+ monocytes were isolated from healthy term (n = 10) and preterm infants (<30 weeks gestational age, n = 33) by MACS technology. Monocyte RNA was sequenced and gene expression was analyzed by Principal Component Analysis and hierarchical clustering. Pathways were identified by Ingenuity Pathway Analysis. Inflammatory proteins were measured by Multiplex ELISA, and plasma S100A proteins by mass spectrometry. Histological chorioamnionitis (HCA) and fetal inflammatory response syndrome (FIRS) were diagnosed by placenta histological examination.Results: S100A8, S100A9, and S100A12 gene expression was significantly increased and with a wider range in preterm vs. term infants. High S100A8 and S100A9 gene expression (n = 17) within the preterm group was strongly associated with spontaneous onset of delivery, HCA, FIRS and elevated inflammatory proteins in cord blood, while low expression (n = 16) was associated with impaired fetal growth and physician-initiated delivery. S100A8 and S100A9 protein levels were significantly lower in preterm vs. term infants, but within the preterm group high S100A gene expression, spontaneous onset of labor, HCA and FIRS were associated with elevated protein levels. One thousand nine hundred genes were differentially expressed in preterm infants with high vs. low S100A alarmin expression. Analysis of 124 genes differentially expressed in S100A high as well as FIRS and HCA groups identified 18 common pathways and S100A alarmins represented major hubs in network analyses.Conclusion: High expression of S100A alarmins in cord blood monocytes identifies a distinct clinical risk group of preterm infants exposed to chorioamnionitis and with a fetal inflammatory response. Gene and pathway analyses suggest that high S100A alarmin expression also affects monocyte function. The connection with monocyte phenotype and inflammation-stimulated S100A expression in other cell types (e.g., neutrophils) warrants further investigation.https://www.frontiersin.org/article/10.3389/fimmu.2020.01194/fullalarminsS100A8S100A9preterm birthchorioamnionitisfetal inflammation |
| spellingShingle | Veronika Golubinskaya Henri Puttonen Ing-Marie Fyhr Halfdan Rydbeck Ann Hellström Bo Jacobsson Bo Jacobsson Bo Jacobsson Holger Nilsson Carina Mallard Karin Sävman Karin Sävman Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm Infants Frontiers in Immunology alarmins S100A8 S100A9 preterm birth chorioamnionitis fetal inflammation |
| title | Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm Infants |
| title_full | Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm Infants |
| title_fullStr | Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm Infants |
| title_full_unstemmed | Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm Infants |
| title_short | Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal Inflammation in Preterm Infants |
| title_sort | expression of s100a alarmins in cord blood monocytes is highly associated with chorioamnionitis and fetal inflammation in preterm infants |
| topic | alarmins S100A8 S100A9 preterm birth chorioamnionitis fetal inflammation |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01194/full |
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