Cargando…

Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone

The blood–brain barrier (BBB), an interface between the systemic circulation and the nervous system, can be a target of cytokines in inflammatory conditions. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induce damage in brain endothelial cells and BBB dysfunc...

Descripción completa

Detalles Bibliográficos
Autores principales: Harazin, András, Bocsik, Alexandra, Barna, Lilla, Kincses, András, Váradi, Judit, Fenyvesi, Ferenc, Tubak, Vilmos, Deli, Maria A., Vecsernyés, Miklós
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958884/
https://www.ncbi.nlm.nih.gov/pubmed/29780671
http://dx.doi.org/10.7717/peerj.4774
_version_ 1783324301062045696
author Harazin, András
Bocsik, Alexandra
Barna, Lilla
Kincses, András
Váradi, Judit
Fenyvesi, Ferenc
Tubak, Vilmos
Deli, Maria A.
Vecsernyés, Miklós
author_facet Harazin, András
Bocsik, Alexandra
Barna, Lilla
Kincses, András
Váradi, Judit
Fenyvesi, Ferenc
Tubak, Vilmos
Deli, Maria A.
Vecsernyés, Miklós
author_sort Harazin, András
collection PubMed
description The blood–brain barrier (BBB), an interface between the systemic circulation and the nervous system, can be a target of cytokines in inflammatory conditions. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induce damage in brain endothelial cells and BBB dysfunction which contribute to neuronal injury. The neuroprotective effects of α-melanocyte stimulating hormone (α-MSH) were investigated in experimental models, but there are no data related to the BBB. Based on our recent study, in which α-MSH reduced barrier dysfunction in human intestinal epithelial cells induced by TNF-α and IL-1β, we hypothesized a protective effect of α-MSH on brain endothelial cells. We examined the effect of these two pro-inflammatory cytokines, and the neuropeptide α-MSH on a culture model of the BBB, primary rat brain endothelial cells co-cultured with rat brain pericytes and glial cells. We demonstrated the expression of melanocortin-1 receptor in isolated rat brain microvessels and cultured brain endothelial cells by RT-PCR and immunohistochemistry. TNF-α and IL-1β induced cell damage, measured by impedance and MTT assay, which was attenuated by α-MSH (1 and 10 pM). The peptide inhibited the cytokine-induced increase in brain endothelial permeability, and restored the morphological changes in cellular junctions visualized by immunostaining for claudin-5 and β-catenin. Elevated production of reactive oxygen species and the nuclear translocation of NF-κB were also reduced by α-MSH in brain endothelial cells stimulated by cytokines. We demonstrated for the first time the direct beneficial effect of α-MSH on cultured brain endothelial cells, indicating that this neurohormone may be protective at the BBB.
format Online
Article
Text
id pubmed-5958884
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher PeerJ Inc.
record_format MEDLINE/PubMed
spelling pubmed-59588842018-05-18 Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone Harazin, András Bocsik, Alexandra Barna, Lilla Kincses, András Váradi, Judit Fenyvesi, Ferenc Tubak, Vilmos Deli, Maria A. Vecsernyés, Miklós PeerJ Cell Biology The blood–brain barrier (BBB), an interface between the systemic circulation and the nervous system, can be a target of cytokines in inflammatory conditions. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induce damage in brain endothelial cells and BBB dysfunction which contribute to neuronal injury. The neuroprotective effects of α-melanocyte stimulating hormone (α-MSH) were investigated in experimental models, but there are no data related to the BBB. Based on our recent study, in which α-MSH reduced barrier dysfunction in human intestinal epithelial cells induced by TNF-α and IL-1β, we hypothesized a protective effect of α-MSH on brain endothelial cells. We examined the effect of these two pro-inflammatory cytokines, and the neuropeptide α-MSH on a culture model of the BBB, primary rat brain endothelial cells co-cultured with rat brain pericytes and glial cells. We demonstrated the expression of melanocortin-1 receptor in isolated rat brain microvessels and cultured brain endothelial cells by RT-PCR and immunohistochemistry. TNF-α and IL-1β induced cell damage, measured by impedance and MTT assay, which was attenuated by α-MSH (1 and 10 pM). The peptide inhibited the cytokine-induced increase in brain endothelial permeability, and restored the morphological changes in cellular junctions visualized by immunostaining for claudin-5 and β-catenin. Elevated production of reactive oxygen species and the nuclear translocation of NF-κB were also reduced by α-MSH in brain endothelial cells stimulated by cytokines. We demonstrated for the first time the direct beneficial effect of α-MSH on cultured brain endothelial cells, indicating that this neurohormone may be protective at the BBB. PeerJ Inc. 2018-05-15 /pmc/articles/PMC5958884/ /pubmed/29780671 http://dx.doi.org/10.7717/peerj.4774 Text en © 2018 Harazin et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Cell Biology
Harazin, András
Bocsik, Alexandra
Barna, Lilla
Kincses, András
Váradi, Judit
Fenyvesi, Ferenc
Tubak, Vilmos
Deli, Maria A.
Vecsernyés, Miklós
Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone
title Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone
title_full Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone
title_fullStr Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone
title_full_unstemmed Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone
title_short Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone
title_sort protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958884/
https://www.ncbi.nlm.nih.gov/pubmed/29780671
http://dx.doi.org/10.7717/peerj.4774
work_keys_str_mv AT harazinandras protectionofculturedbrainendothelialcellsfromcytokineinduceddamagebyamelanocytestimulatinghormone
AT bocsikalexandra protectionofculturedbrainendothelialcellsfromcytokineinduceddamagebyamelanocytestimulatinghormone
AT barnalilla protectionofculturedbrainendothelialcellsfromcytokineinduceddamagebyamelanocytestimulatinghormone
AT kincsesandras protectionofculturedbrainendothelialcellsfromcytokineinduceddamagebyamelanocytestimulatinghormone
AT varadijudit protectionofculturedbrainendothelialcellsfromcytokineinduceddamagebyamelanocytestimulatinghormone
AT fenyvesiferenc protectionofculturedbrainendothelialcellsfromcytokineinduceddamagebyamelanocytestimulatinghormone
AT tubakvilmos protectionofculturedbrainendothelialcellsfromcytokineinduceddamagebyamelanocytestimulatinghormone
AT delimariaa protectionofculturedbrainendothelialcellsfromcytokineinduceddamagebyamelanocytestimulatinghormone
AT vecsernyesmiklos protectionofculturedbrainendothelialcellsfromcytokineinduceddamagebyamelanocytestimulatinghormone