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Secretome of Hypoxic Endothelial Cells Stimulates Bone Marrow-Derived Mesenchymal Stem Cells to Enhance Alternative Activation of Macrophages

We intended to explore the cellular interaction between mesenchymal stem cells (MSCs) and injured endothelial cells leading to macrophage alternative polarization in healing kidney ischemic reperfusion injury. In vivo, the amounts of recruited macrophages were significantly mitigated by MSCs in the...

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Autores principales: Chou, Kang-Ju, Hsu, Chih-Yang, Huang, Chien-Wei, Chen, Hsin-Yu, Ou, Shih-Hsiang, Chen, Chien-Liang, Lee, Po-Tsang, Fang, Hua-Chang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352547/
https://www.ncbi.nlm.nih.gov/pubmed/32575834
http://dx.doi.org/10.3390/ijms21124409
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author Chou, Kang-Ju
Hsu, Chih-Yang
Huang, Chien-Wei
Chen, Hsin-Yu
Ou, Shih-Hsiang
Chen, Chien-Liang
Lee, Po-Tsang
Fang, Hua-Chang
author_facet Chou, Kang-Ju
Hsu, Chih-Yang
Huang, Chien-Wei
Chen, Hsin-Yu
Ou, Shih-Hsiang
Chen, Chien-Liang
Lee, Po-Tsang
Fang, Hua-Chang
author_sort Chou, Kang-Ju
collection PubMed
description We intended to explore the cellular interaction between mesenchymal stem cells (MSCs) and injured endothelial cells leading to macrophage alternative polarization in healing kidney ischemic reperfusion injury. In vivo, the amounts of recruited macrophages were significantly mitigated by MSCs in the injured tissues, especially in the group using hematopoietic cell E- and L-selectin ligand (HCELL)-positive MSCs. Compared to controls, MSCs also enhanced expression of CD206 and CD163, which was further enhanced by HCELL expression. In vitro, analysis of cytokines involving macrophage polarization showed IL-13 rather than IL-4 from MSCs agreed with expression of macrophage CD206 in the presence of hypoxic endothelial cells. Among them, HCELL-positive MSCs in contact with hypoxic endothelial cells produced the greatest response, which were reduced without HCELL or using a transwell to prevent cell contact. With blockade of the respective cytokine, downregulated MSCs secretion of IL-13 and CD206 expression were observed using inhibitors of IFN-γ and TNF-α, but not using those of TGF-β and NO. With IFN-γ and TNF-α, MSCs IL-13 secretion and CD206 expression were upregulated. In conclusion, hypoxia induces endothelial cells producing multiple cytokines. Among them, IFN-γ and TNF-α that stimulate MSCs to secrete IL-13 but not IL-4, leading to alternative polarization.
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spelling pubmed-73525472020-07-15 Secretome of Hypoxic Endothelial Cells Stimulates Bone Marrow-Derived Mesenchymal Stem Cells to Enhance Alternative Activation of Macrophages Chou, Kang-Ju Hsu, Chih-Yang Huang, Chien-Wei Chen, Hsin-Yu Ou, Shih-Hsiang Chen, Chien-Liang Lee, Po-Tsang Fang, Hua-Chang Int J Mol Sci Article We intended to explore the cellular interaction between mesenchymal stem cells (MSCs) and injured endothelial cells leading to macrophage alternative polarization in healing kidney ischemic reperfusion injury. In vivo, the amounts of recruited macrophages were significantly mitigated by MSCs in the injured tissues, especially in the group using hematopoietic cell E- and L-selectin ligand (HCELL)-positive MSCs. Compared to controls, MSCs also enhanced expression of CD206 and CD163, which was further enhanced by HCELL expression. In vitro, analysis of cytokines involving macrophage polarization showed IL-13 rather than IL-4 from MSCs agreed with expression of macrophage CD206 in the presence of hypoxic endothelial cells. Among them, HCELL-positive MSCs in contact with hypoxic endothelial cells produced the greatest response, which were reduced without HCELL or using a transwell to prevent cell contact. With blockade of the respective cytokine, downregulated MSCs secretion of IL-13 and CD206 expression were observed using inhibitors of IFN-γ and TNF-α, but not using those of TGF-β and NO. With IFN-γ and TNF-α, MSCs IL-13 secretion and CD206 expression were upregulated. In conclusion, hypoxia induces endothelial cells producing multiple cytokines. Among them, IFN-γ and TNF-α that stimulate MSCs to secrete IL-13 but not IL-4, leading to alternative polarization. MDPI 2020-06-21 /pmc/articles/PMC7352547/ /pubmed/32575834 http://dx.doi.org/10.3390/ijms21124409 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chou, Kang-Ju
Hsu, Chih-Yang
Huang, Chien-Wei
Chen, Hsin-Yu
Ou, Shih-Hsiang
Chen, Chien-Liang
Lee, Po-Tsang
Fang, Hua-Chang
Secretome of Hypoxic Endothelial Cells Stimulates Bone Marrow-Derived Mesenchymal Stem Cells to Enhance Alternative Activation of Macrophages
title Secretome of Hypoxic Endothelial Cells Stimulates Bone Marrow-Derived Mesenchymal Stem Cells to Enhance Alternative Activation of Macrophages
title_full Secretome of Hypoxic Endothelial Cells Stimulates Bone Marrow-Derived Mesenchymal Stem Cells to Enhance Alternative Activation of Macrophages
title_fullStr Secretome of Hypoxic Endothelial Cells Stimulates Bone Marrow-Derived Mesenchymal Stem Cells to Enhance Alternative Activation of Macrophages
title_full_unstemmed Secretome of Hypoxic Endothelial Cells Stimulates Bone Marrow-Derived Mesenchymal Stem Cells to Enhance Alternative Activation of Macrophages
title_short Secretome of Hypoxic Endothelial Cells Stimulates Bone Marrow-Derived Mesenchymal Stem Cells to Enhance Alternative Activation of Macrophages
title_sort secretome of hypoxic endothelial cells stimulates bone marrow-derived mesenchymal stem cells to enhance alternative activation of macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352547/
https://www.ncbi.nlm.nih.gov/pubmed/32575834
http://dx.doi.org/10.3390/ijms21124409
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