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Effect of bone marrow mesenchymal stem cells on the polarization of macrophages

Inflammation is a defensive response in the living tissue of the vascular system that acts against damage factors and involves various types of immune cells, including macrophages, neutrophils, endothelial cells and other associated immune molecules. If the release of inflammatory mediators is exces...

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Autores principales: Zheng, Yuan Hua, Deng, Yi Yu, Lai, Wen, Zheng, Shao Yi, Bian, Hui Ning, Liu, Zu An, Huang, Zhi Feng, Sun, Chuan Wei, Li, Han Hua, Luo, Hong Min, Ma, Liang Hua, Chen, Han Xi, Xiong, Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802220/
https://www.ncbi.nlm.nih.gov/pubmed/29363724
http://dx.doi.org/10.3892/mmr.2018.8457
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author Zheng, Yuan Hua
Deng, Yi Yu
Lai, Wen
Zheng, Shao Yi
Bian, Hui Ning
Liu, Zu An
Huang, Zhi Feng
Sun, Chuan Wei
Li, Han Hua
Luo, Hong Min
Ma, Liang Hua
Chen, Han Xi
Xiong, Bing
author_facet Zheng, Yuan Hua
Deng, Yi Yu
Lai, Wen
Zheng, Shao Yi
Bian, Hui Ning
Liu, Zu An
Huang, Zhi Feng
Sun, Chuan Wei
Li, Han Hua
Luo, Hong Min
Ma, Liang Hua
Chen, Han Xi
Xiong, Bing
author_sort Zheng, Yuan Hua
collection PubMed
description Inflammation is a defensive response in the living tissue of the vascular system that acts against damage factors and involves various types of immune cells, including macrophages, neutrophils, endothelial cells and other associated immune molecules. If the release of inflammatory mediators is excessive, systemic inflammatory response syndrome may develop. Sepsis is the most common complication of severe burns and is a systemic inflammatory response syndrome that is caused by infectious factors and is capable of leading to multiple organ dysfunction and potentially death. Research concerning the mechanism and treatment of sepsis is crucial. Macrophages are an important type of immune cell that remove invasive pathogens and are involved in innate and adaptive immune responses. It has been previously reported that bone marrow mesenchymal stem cells (BMSCs) affect macrophages by regulating immunity. The present study aimed to investigate the effect of BMSCs on macrophage polarization in vivo and in vitro, in addition to the potential therapeutic effect of these cells on experimental sepsis. BMSCs and peritoneal macrophages were isolated from Sprague-Dawley rats and co-cultured overnight as a mixed culture or Transwell system, and subsequently stimulated with 100 ng/ml lipopolysaccharide (LPS). After 12 h, the medium was replaced with normal complete medium for various durations and supernatants were collected to extract proteins and cells for ELISA, western blot and flow cytometry analysis to investigate different aspects of macrophages. Sepsis was induced in Sprague-Dawley rats by injection of LPS (5 mg/kg), followed by tail vein injection of BMSCs or PBS 1 h later. After 6, 12, 24 and 48 h, lung tissues were harvested for pathological observation and peritoneal macrophages were collected for flow cytometry analysis to assess the expression of markers, including cluster of differentiation (CD)68 (used for gating), CD11c and CD206. The results demonstrated that, in the culture medium, LPS stimulation increased the expression of CD11c in macrophages, and the levels of tumor necrosis factor-α and inducible nitric oxide synthase were also increased. By contrast, in macrophages treated with BMSCs directly, the expression of CD11c was reduced compared with the LPS-stimulated macrophage alone group. However, the secretion of interleukin-10, transforming growth factor-β and arginase-1 was increased in the direct co-culture group, compared with the LPS-stimulated macrophage alone group. BMSCs reduced the inflammation in lung tissues and inhibited macrophage expression of CD11c in the rat model of sepsis. The results of the present study demonstrated that BMSCs co-cultured with macrophages directly inhibited macrophage differentiation into the M1 phenotype and reduced inflammation in macrophages stimulated by LPS. In vivo, BMSCs decreased the expression of CD11c in peritoneal macrophages and reduced the pathological inflammatory response in the lungs. The findings of the present study demonstrated that BMSCs may reduce the extent of the systemic inflammatory response, which may contribute to the development for a novel type of treatment for sepsis in the future.
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spelling pubmed-58022202018-02-26 Effect of bone marrow mesenchymal stem cells on the polarization of macrophages Zheng, Yuan Hua Deng, Yi Yu Lai, Wen Zheng, Shao Yi Bian, Hui Ning Liu, Zu An Huang, Zhi Feng Sun, Chuan Wei Li, Han Hua Luo, Hong Min Ma, Liang Hua Chen, Han Xi Xiong, Bing Mol Med Rep Articles Inflammation is a defensive response in the living tissue of the vascular system that acts against damage factors and involves various types of immune cells, including macrophages, neutrophils, endothelial cells and other associated immune molecules. If the release of inflammatory mediators is excessive, systemic inflammatory response syndrome may develop. Sepsis is the most common complication of severe burns and is a systemic inflammatory response syndrome that is caused by infectious factors and is capable of leading to multiple organ dysfunction and potentially death. Research concerning the mechanism and treatment of sepsis is crucial. Macrophages are an important type of immune cell that remove invasive pathogens and are involved in innate and adaptive immune responses. It has been previously reported that bone marrow mesenchymal stem cells (BMSCs) affect macrophages by regulating immunity. The present study aimed to investigate the effect of BMSCs on macrophage polarization in vivo and in vitro, in addition to the potential therapeutic effect of these cells on experimental sepsis. BMSCs and peritoneal macrophages were isolated from Sprague-Dawley rats and co-cultured overnight as a mixed culture or Transwell system, and subsequently stimulated with 100 ng/ml lipopolysaccharide (LPS). After 12 h, the medium was replaced with normal complete medium for various durations and supernatants were collected to extract proteins and cells for ELISA, western blot and flow cytometry analysis to investigate different aspects of macrophages. Sepsis was induced in Sprague-Dawley rats by injection of LPS (5 mg/kg), followed by tail vein injection of BMSCs or PBS 1 h later. After 6, 12, 24 and 48 h, lung tissues were harvested for pathological observation and peritoneal macrophages were collected for flow cytometry analysis to assess the expression of markers, including cluster of differentiation (CD)68 (used for gating), CD11c and CD206. The results demonstrated that, in the culture medium, LPS stimulation increased the expression of CD11c in macrophages, and the levels of tumor necrosis factor-α and inducible nitric oxide synthase were also increased. By contrast, in macrophages treated with BMSCs directly, the expression of CD11c was reduced compared with the LPS-stimulated macrophage alone group. However, the secretion of interleukin-10, transforming growth factor-β and arginase-1 was increased in the direct co-culture group, compared with the LPS-stimulated macrophage alone group. BMSCs reduced the inflammation in lung tissues and inhibited macrophage expression of CD11c in the rat model of sepsis. The results of the present study demonstrated that BMSCs co-cultured with macrophages directly inhibited macrophage differentiation into the M1 phenotype and reduced inflammation in macrophages stimulated by LPS. In vivo, BMSCs decreased the expression of CD11c in peritoneal macrophages and reduced the pathological inflammatory response in the lungs. The findings of the present study demonstrated that BMSCs may reduce the extent of the systemic inflammatory response, which may contribute to the development for a novel type of treatment for sepsis in the future. D.A. Spandidos 2018-03 2018-01-18 /pmc/articles/PMC5802220/ /pubmed/29363724 http://dx.doi.org/10.3892/mmr.2018.8457 Text en Copyright: © Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zheng, Yuan Hua
Deng, Yi Yu
Lai, Wen
Zheng, Shao Yi
Bian, Hui Ning
Liu, Zu An
Huang, Zhi Feng
Sun, Chuan Wei
Li, Han Hua
Luo, Hong Min
Ma, Liang Hua
Chen, Han Xi
Xiong, Bing
Effect of bone marrow mesenchymal stem cells on the polarization of macrophages
title Effect of bone marrow mesenchymal stem cells on the polarization of macrophages
title_full Effect of bone marrow mesenchymal stem cells on the polarization of macrophages
title_fullStr Effect of bone marrow mesenchymal stem cells on the polarization of macrophages
title_full_unstemmed Effect of bone marrow mesenchymal stem cells on the polarization of macrophages
title_short Effect of bone marrow mesenchymal stem cells on the polarization of macrophages
title_sort effect of bone marrow mesenchymal stem cells on the polarization of macrophages
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802220/
https://www.ncbi.nlm.nih.gov/pubmed/29363724
http://dx.doi.org/10.3892/mmr.2018.8457
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