Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells
Following an intraventricular hemorrhage (IVH), red blood cell lysis and hemoglobin (Hb) oxidation with the release of heme can cause sterile neuroinflammation. In this study, we measured Hb derivates and cellular adhesion molecules ICAM-1 and VCAM-1 with cell-free miRNAs in cerebrospinal fluid (CSF...
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doaj-81c716040f5c441387ec8700418f13692021-08-26T13:52:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-01228648864810.3390/ijms22168648Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial CellsZsolt Fejes0Marianna Pócsi1Jun Takai2Judit Erdei3Andrea Tóth4Enikő Balogh5Ágnes Rusznyák6Ferenc Fenyvesi7Andrea Nagy8János Kappelmayer9Viktória Jeney10Béla Nagy11Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Laboratory Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Laboratory Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryMTA-DE Lendület Vascular Pathophysiology Research Group, Research Centre for Molecular Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryMTA-DE Lendület Vascular Pathophysiology Research Group, Research Centre for Molecular Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryMTA-DE Lendület Vascular Pathophysiology Research Group, Research Centre for Molecular Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pharmaceutical Technologies, Faculty of Pharmacy, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pharmaceutical Technologies, Faculty of Pharmacy, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pediatrics, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Laboratory Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryMTA-DE Lendület Vascular Pathophysiology Research Group, Research Centre for Molecular Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Laboratory Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryFollowing an intraventricular hemorrhage (IVH), red blood cell lysis and hemoglobin (Hb) oxidation with the release of heme can cause sterile neuroinflammation. In this study, we measured Hb derivates and cellular adhesion molecules ICAM-1 and VCAM-1 with cell-free miRNAs in cerebrospinal fluid (CSF) samples obtained from Grade-III and Grade-IV preterm IVH infants (IVH-III and IVH-IV, respectively) at multiple time points between days 0–60 after the onset of IVH. Furthermore, human choroid plexus epithelial cells (HCPEpiCs) were incubated with IVH and non-IVH CSF (10 <i>v</i>/<i>v</i> %) for 24 h in vitro to investigate the IVH-induced inflammatory response that was investigated via: (i) HMOX1, IL8, VCAM1, and ICAM1 mRNAs as well as miR-155, miR-223, and miR-181b levels by RT-qPCR; (ii) nuclear translocation of the NF-κB p65 subunit by fluorescence microscopy; and (iii) reactive oxygen species (ROS) measurement. We found a time-dependent alteration of heme, IL-8, and adhesion molecules which revealed a prolonged elevation in IVH-IV vs. IVH-III with higher miR-155 and miR-181b expression at days 41–60. Exposure of HCPEpiCs to IVH CSF samples induced HMOX1, IL8, and ICAM1 mRNA levels along with increased ROS production via the NF-κB pathway activation but without cell death, as confirmed by the cell viability assay. Additionally, the enhanced intracellular miR-155 level was accompanied by lower miR-223 and miR-181b expression in HCPEpiCs after CSF treatment. Overall, choroid plexus epithelial cells exhibit an abnormal cell phenotype after interaction with pro-inflammatory CSF of IVH origin which may contribute to the development of later clinical complications in preterm IVH.https://www.mdpi.com/1422-0067/22/16/8648cerebrospinal fluidchoroid plexus epithelial cellhemeinflammationintraventricular hemorrhagemicroRNA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zsolt Fejes Marianna Pócsi Jun Takai Judit Erdei Andrea Tóth Enikő Balogh Ágnes Rusznyák Ferenc Fenyvesi Andrea Nagy János Kappelmayer Viktória Jeney Béla Nagy |
spellingShingle |
Zsolt Fejes Marianna Pócsi Jun Takai Judit Erdei Andrea Tóth Enikő Balogh Ágnes Rusznyák Ferenc Fenyvesi Andrea Nagy János Kappelmayer Viktória Jeney Béla Nagy Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells International Journal of Molecular Sciences cerebrospinal fluid choroid plexus epithelial cell heme inflammation intraventricular hemorrhage microRNA |
author_facet |
Zsolt Fejes Marianna Pócsi Jun Takai Judit Erdei Andrea Tóth Enikő Balogh Ágnes Rusznyák Ferenc Fenyvesi Andrea Nagy János Kappelmayer Viktória Jeney Béla Nagy |
author_sort |
Zsolt Fejes |
title |
Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells |
title_short |
Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells |
title_full |
Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells |
title_fullStr |
Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells |
title_full_unstemmed |
Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells |
title_sort |
preterm intraventricular hemorrhage-induced inflammatory response in human choroid plexus epithelial cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-08-01 |
description |
Following an intraventricular hemorrhage (IVH), red blood cell lysis and hemoglobin (Hb) oxidation with the release of heme can cause sterile neuroinflammation. In this study, we measured Hb derivates and cellular adhesion molecules ICAM-1 and VCAM-1 with cell-free miRNAs in cerebrospinal fluid (CSF) samples obtained from Grade-III and Grade-IV preterm IVH infants (IVH-III and IVH-IV, respectively) at multiple time points between days 0–60 after the onset of IVH. Furthermore, human choroid plexus epithelial cells (HCPEpiCs) were incubated with IVH and non-IVH CSF (10 <i>v</i>/<i>v</i> %) for 24 h in vitro to investigate the IVH-induced inflammatory response that was investigated via: (i) HMOX1, IL8, VCAM1, and ICAM1 mRNAs as well as miR-155, miR-223, and miR-181b levels by RT-qPCR; (ii) nuclear translocation of the NF-κB p65 subunit by fluorescence microscopy; and (iii) reactive oxygen species (ROS) measurement. We found a time-dependent alteration of heme, IL-8, and adhesion molecules which revealed a prolonged elevation in IVH-IV vs. IVH-III with higher miR-155 and miR-181b expression at days 41–60. Exposure of HCPEpiCs to IVH CSF samples induced HMOX1, IL8, and ICAM1 mRNA levels along with increased ROS production via the NF-κB pathway activation but without cell death, as confirmed by the cell viability assay. Additionally, the enhanced intracellular miR-155 level was accompanied by lower miR-223 and miR-181b expression in HCPEpiCs after CSF treatment. Overall, choroid plexus epithelial cells exhibit an abnormal cell phenotype after interaction with pro-inflammatory CSF of IVH origin which may contribute to the development of later clinical complications in preterm IVH. |
topic |
cerebrospinal fluid choroid plexus epithelial cell heme inflammation intraventricular hemorrhage microRNA |
url |
https://www.mdpi.com/1422-0067/22/16/8648 |
work_keys_str_mv |
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