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A role for human brain pericytes in neuroinflammation

BACKGROUND: Brain inflammation plays a key role in neurological disease. Although much research has been conducted investigating inflammatory events in animal models, potential differences in human brain versus rodent models makes it imperative that we also study these phenomena in human cells and t...

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Autores principales: Jansson, Deidre, Rustenhoven, Justin, Feng, Sheryl, Hurley, Daniel, Oldfield, Robyn L, Bergin, Peter S, Mee, Edward W, Faull, Richard LM, Dragunow, Mike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105169/
https://www.ncbi.nlm.nih.gov/pubmed/24920309
http://dx.doi.org/10.1186/1742-2094-11-104
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author Jansson, Deidre
Rustenhoven, Justin
Feng, Sheryl
Hurley, Daniel
Oldfield, Robyn L
Bergin, Peter S
Mee, Edward W
Faull, Richard LM
Dragunow, Mike
author_facet Jansson, Deidre
Rustenhoven, Justin
Feng, Sheryl
Hurley, Daniel
Oldfield, Robyn L
Bergin, Peter S
Mee, Edward W
Faull, Richard LM
Dragunow, Mike
author_sort Jansson, Deidre
collection PubMed
description BACKGROUND: Brain inflammation plays a key role in neurological disease. Although much research has been conducted investigating inflammatory events in animal models, potential differences in human brain versus rodent models makes it imperative that we also study these phenomena in human cells and tissue. METHODS: Primary human brain cell cultures were generated from biopsy tissue of patients undergoing surgery for drug-resistant epilepsy. Cells were treated with pro-inflammatory compounds IFNγ, TNFα, IL-1β, and LPS, and chemokines IP-10 and MCP-1 were measured by immunocytochemistry, western blot, and qRT-PCR. Microarray analysis was also performed on late passage cultures treated with vehicle or IFNγ and IL-1β. RESULTS: Early passage human brain cell cultures were a mixture of microglia, astrocytes, fibroblasts and pericytes. Later passage cultures contained proliferating fibroblasts and pericytes only. Under basal culture conditions all cell types showed cytoplasmic NFκB indicating that they were in a non-activated state. Expression of IP-10 and MCP-1 were significantly increased in response to pro-inflammatory stimuli. The two chemokines were expressed in mixed cultures as well as cultures of fibroblasts and pericytes only. The expression of IP-10 and MCP-1 were regulated at the mRNA and protein level, and both were secreted into cell culture media. NFκB nuclear translocation was also detected in response to pro-inflammatory cues (except IFNγ) in all cell types. Microarray analysis of brain pericytes also revealed widespread changes in gene expression in response to the combination of IFNγ and IL-1β treatment including interleukins, chemokines, cellular adhesion molecules and much more. CONCLUSIONS: Adult human brain cells are sensitive to cytokine challenge. As expected ‘classical’ brain immune cells, such as microglia and astrocytes, responded to cytokine challenge but of even more interest, brain pericytes also responded to such challenge with a rich repertoire of gene expression. Immune activation of brain pericytes may play an important role in communicating inflammatory signals to and within the brain interior and may also be involved in blood brain barrier (BBB) disruption . Targeting brain pericytes, as well as microglia and astrocytes, may provide novel opportunities for reducing brain inflammation and maintaining BBB function and brain homeostasis in human brain disease.
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spelling pubmed-41051692014-07-22 A role for human brain pericytes in neuroinflammation Jansson, Deidre Rustenhoven, Justin Feng, Sheryl Hurley, Daniel Oldfield, Robyn L Bergin, Peter S Mee, Edward W Faull, Richard LM Dragunow, Mike J Neuroinflammation Research BACKGROUND: Brain inflammation plays a key role in neurological disease. Although much research has been conducted investigating inflammatory events in animal models, potential differences in human brain versus rodent models makes it imperative that we also study these phenomena in human cells and tissue. METHODS: Primary human brain cell cultures were generated from biopsy tissue of patients undergoing surgery for drug-resistant epilepsy. Cells were treated with pro-inflammatory compounds IFNγ, TNFα, IL-1β, and LPS, and chemokines IP-10 and MCP-1 were measured by immunocytochemistry, western blot, and qRT-PCR. Microarray analysis was also performed on late passage cultures treated with vehicle or IFNγ and IL-1β. RESULTS: Early passage human brain cell cultures were a mixture of microglia, astrocytes, fibroblasts and pericytes. Later passage cultures contained proliferating fibroblasts and pericytes only. Under basal culture conditions all cell types showed cytoplasmic NFκB indicating that they were in a non-activated state. Expression of IP-10 and MCP-1 were significantly increased in response to pro-inflammatory stimuli. The two chemokines were expressed in mixed cultures as well as cultures of fibroblasts and pericytes only. The expression of IP-10 and MCP-1 were regulated at the mRNA and protein level, and both were secreted into cell culture media. NFκB nuclear translocation was also detected in response to pro-inflammatory cues (except IFNγ) in all cell types. Microarray analysis of brain pericytes also revealed widespread changes in gene expression in response to the combination of IFNγ and IL-1β treatment including interleukins, chemokines, cellular adhesion molecules and much more. CONCLUSIONS: Adult human brain cells are sensitive to cytokine challenge. As expected ‘classical’ brain immune cells, such as microglia and astrocytes, responded to cytokine challenge but of even more interest, brain pericytes also responded to such challenge with a rich repertoire of gene expression. Immune activation of brain pericytes may play an important role in communicating inflammatory signals to and within the brain interior and may also be involved in blood brain barrier (BBB) disruption . Targeting brain pericytes, as well as microglia and astrocytes, may provide novel opportunities for reducing brain inflammation and maintaining BBB function and brain homeostasis in human brain disease. BioMed Central 2014-06-11 /pmc/articles/PMC4105169/ /pubmed/24920309 http://dx.doi.org/10.1186/1742-2094-11-104 Text en Copyright © 2014 Jansson et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Jansson, Deidre
Rustenhoven, Justin
Feng, Sheryl
Hurley, Daniel
Oldfield, Robyn L
Bergin, Peter S
Mee, Edward W
Faull, Richard LM
Dragunow, Mike
A role for human brain pericytes in neuroinflammation
title A role for human brain pericytes in neuroinflammation
title_full A role for human brain pericytes in neuroinflammation
title_fullStr A role for human brain pericytes in neuroinflammation
title_full_unstemmed A role for human brain pericytes in neuroinflammation
title_short A role for human brain pericytes in neuroinflammation
title_sort role for human brain pericytes in neuroinflammation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105169/
https://www.ncbi.nlm.nih.gov/pubmed/24920309
http://dx.doi.org/10.1186/1742-2094-11-104
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