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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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Autores principales: Fejes, Zsolt, Pócsi, Marianna, Takai, Jun, Erdei, Judit, Tóth, Andrea, Balogh, Enikő, Rusznyák, Ágnes, Fenyvesi, Ferenc, Nagy, Andrea, Kappelmayer, János, Jeney, Viktória, Nagy, Béla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395401/
https://www.ncbi.nlm.nih.gov/pubmed/34445350
http://dx.doi.org/10.3390/ijms22168648
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author Fejes, Zsolt
Pócsi, Marianna
Takai, Jun
Erdei, Judit
Tóth, Andrea
Balogh, Enikő
Rusznyák, Ágnes
Fenyvesi, Ferenc
Nagy, Andrea
Kappelmayer, János
Jeney, Viktória
Nagy, Béla
author_facet Fejes, Zsolt
Pócsi, Marianna
Takai, Jun
Erdei, Judit
Tóth, Andrea
Balogh, Enikő
Rusznyák, Ágnes
Fenyvesi, Ferenc
Nagy, Andrea
Kappelmayer, János
Jeney, Viktória
Nagy, Béla
author_sort Fejes, Zsolt
collection PubMed
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 v/v %) 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.
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spelling pubmed-83954012021-08-28 Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells Fejes, Zsolt Pócsi, Marianna Takai, Jun Erdei, Judit Tóth, Andrea Balogh, Enikő Rusznyák, Ágnes Fenyvesi, Ferenc Nagy, Andrea Kappelmayer, János Jeney, Viktória Nagy, Béla Int J Mol Sci Article 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 v/v %) 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. MDPI 2021-08-11 /pmc/articles/PMC8395401/ /pubmed/34445350 http://dx.doi.org/10.3390/ijms22168648 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fejes, Zsolt
Pócsi, Marianna
Takai, Jun
Erdei, Judit
Tóth, Andrea
Balogh, Enikő
Rusznyák, Ágnes
Fenyvesi, Ferenc
Nagy, Andrea
Kappelmayer, János
Jeney, Viktória
Nagy, Béla
Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395401/
https://www.ncbi.nlm.nih.gov/pubmed/34445350
http://dx.doi.org/10.3390/ijms22168648
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