Maslinic acid alleviates ischemia/reperfusion-induced inflammation by downregulation of NFκB-mediated adhesion molecule expression

Ischemia/reperfusion (I/R)-induced inflammation is associated with enhanced leukocyte rolling, adhesion and transmigration within the microcirculation. These steps are mediated by hypoxia-triggered signaling pathways, which upregulate adhesion molecule expression on endothelial cells and pericytes....

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Autores principales: Ampofo, Emmanuel, Berg, Julian J., Menger, Michael D., Laschke, Matthias W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467883/
https://www.ncbi.nlm.nih.gov/pubmed/30992483
http://dx.doi.org/10.1038/s41598-019-42465-7
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author Ampofo, Emmanuel
Berg, Julian J.
Menger, Michael D.
Laschke, Matthias W.
author_facet Ampofo, Emmanuel
Berg, Julian J.
Menger, Michael D.
Laschke, Matthias W.
author_sort Ampofo, Emmanuel
collection PubMed
description Ischemia/reperfusion (I/R)-induced inflammation is associated with enhanced leukocyte rolling, adhesion and transmigration within the microcirculation. These steps are mediated by hypoxia-triggered signaling pathways, which upregulate adhesion molecule expression on endothelial cells and pericytes. We analyzed whether these cellular events are affected by maslinic acid (MA). Mitochondrial activity and viability of MA-exposed endothelial cells and pericytes were assessed by water-soluble tetrazolium (WST)-1 and lactate dehydrogenase (LDH) assays as well as Annexin V/propidium iodide (PI) stainings. Effects of MA on hypoxia and reoxygenation-induced expression of E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were determined by flow cytometry. The subcellular localization of the NFκB subunit p65 was analyzed by immunofluorescence and Western blot. I/R-induced leukocytic inflammation was studied in MA- and vehicle-treated mouse dorsal skinfold chambers by intravital fluorescence microscopy and immunohistochemistry. MA did not affect viability, but suppressed the mitochondrial activity of endothelial cells. Furthermore, MA reduced adhesion molecule expression on endothelial cells and pericytes due to an inhibitory action on NFκB signaling. Numbers of adherent and transmigrated leukocytes were lower in post-ischemic tissue of MA-treated mice when compared to vehicle-treated controls. In addition, MA affected reactive oxygen species (ROS) formation, resulting in a diminished oxidative DNA damage. Hence, MA represents an attractive compound for the establishment of novel therapeutic approaches against I/R-induced inflammation.
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spelling pubmed-64678832019-04-18 Maslinic acid alleviates ischemia/reperfusion-induced inflammation by downregulation of NFκB-mediated adhesion molecule expression Ampofo, Emmanuel Berg, Julian J. Menger, Michael D. Laschke, Matthias W. Sci Rep Article Ischemia/reperfusion (I/R)-induced inflammation is associated with enhanced leukocyte rolling, adhesion and transmigration within the microcirculation. These steps are mediated by hypoxia-triggered signaling pathways, which upregulate adhesion molecule expression on endothelial cells and pericytes. We analyzed whether these cellular events are affected by maslinic acid (MA). Mitochondrial activity and viability of MA-exposed endothelial cells and pericytes were assessed by water-soluble tetrazolium (WST)-1 and lactate dehydrogenase (LDH) assays as well as Annexin V/propidium iodide (PI) stainings. Effects of MA on hypoxia and reoxygenation-induced expression of E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were determined by flow cytometry. The subcellular localization of the NFκB subunit p65 was analyzed by immunofluorescence and Western blot. I/R-induced leukocytic inflammation was studied in MA- and vehicle-treated mouse dorsal skinfold chambers by intravital fluorescence microscopy and immunohistochemistry. MA did not affect viability, but suppressed the mitochondrial activity of endothelial cells. Furthermore, MA reduced adhesion molecule expression on endothelial cells and pericytes due to an inhibitory action on NFκB signaling. Numbers of adherent and transmigrated leukocytes were lower in post-ischemic tissue of MA-treated mice when compared to vehicle-treated controls. In addition, MA affected reactive oxygen species (ROS) formation, resulting in a diminished oxidative DNA damage. Hence, MA represents an attractive compound for the establishment of novel therapeutic approaches against I/R-induced inflammation. Nature Publishing Group UK 2019-04-16 /pmc/articles/PMC6467883/ /pubmed/30992483 http://dx.doi.org/10.1038/s41598-019-42465-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ampofo, Emmanuel
Berg, Julian J.
Menger, Michael D.
Laschke, Matthias W.
Maslinic acid alleviates ischemia/reperfusion-induced inflammation by downregulation of NFκB-mediated adhesion molecule expression
title Maslinic acid alleviates ischemia/reperfusion-induced inflammation by downregulation of NFκB-mediated adhesion molecule expression
title_full Maslinic acid alleviates ischemia/reperfusion-induced inflammation by downregulation of NFκB-mediated adhesion molecule expression
title_fullStr Maslinic acid alleviates ischemia/reperfusion-induced inflammation by downregulation of NFκB-mediated adhesion molecule expression
title_full_unstemmed Maslinic acid alleviates ischemia/reperfusion-induced inflammation by downregulation of NFκB-mediated adhesion molecule expression
title_short Maslinic acid alleviates ischemia/reperfusion-induced inflammation by downregulation of NFκB-mediated adhesion molecule expression
title_sort maslinic acid alleviates ischemia/reperfusion-induced inflammation by downregulation of nfκb-mediated adhesion molecule expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467883/
https://www.ncbi.nlm.nih.gov/pubmed/30992483
http://dx.doi.org/10.1038/s41598-019-42465-7
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