Peripheral Blood-Derived Mesenchymal Stem Cells Modulate Macrophage Plasticity through the IL-10/STAT3 Pathway

Mesenchymal stem cells (MSCs) are multipotent cells that can skew the balance of M1/M2 macrophage polarization towards the M2 phenotype via their paracrine effects, thereby promoting anatomical and functional recovery after many inflammatory diseases induced by macrophages. However, the underlying m...

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Main Authors: Qi-Ming Pang, Rui Yang, Meng Zhang, Wang-Hui Zou, Nan-Nan Qian, Qi-Jing Xu, Hui Chen, Jia-Chen Peng, Xiao-Ping Luo, Qian Zhang, Tao Zhang
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2022/5181241
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author Qi-Ming Pang
Rui Yang
Meng Zhang
Wang-Hui Zou
Nan-Nan Qian
Qi-Jing Xu
Hui Chen
Jia-Chen Peng
Xiao-Ping Luo
Qian Zhang
Tao Zhang
author_facet Qi-Ming Pang
Rui Yang
Meng Zhang
Wang-Hui Zou
Nan-Nan Qian
Qi-Jing Xu
Hui Chen
Jia-Chen Peng
Xiao-Ping Luo
Qian Zhang
Tao Zhang
author_sort Qi-Ming Pang
collection DOAJ
description Mesenchymal stem cells (MSCs) are multipotent cells that can skew the balance of M1/M2 macrophage polarization towards the M2 phenotype via their paracrine effects, thereby promoting anatomical and functional recovery after many inflammatory diseases induced by macrophages. However, the underlying mechanism is still poorly understood. This study focused on the IL-10/STAT3 pathway and investigated whether IL-10 secreted by PBMSCs could mediate M2 polarization through the activation of this pathway. In this study, a Transwell system was used for coculturing macrophages and PBMSCs. ELISA and RT-qPCR analysis found that PBMSCs and their conditioned media (P-CM) significantly induced the expression of IL-10, while significantly inhibiting the expression of IL-1β and TNF-α; moreover, this effect could be reversed by adding Ab9969 (an IL-10 neutralizing antibody) and Stattic (a STAT3 inhibitor). Furthermore, western blotting and immunofluorescence assays demonstrated that JAK1/STAT3 signaling was significantly upregulated in macrophages cocultured with PBMSCs or P-CM, accompanied by an increase in the M2 biomarker CD206 and a decrease in the M1 biomarker CD86. This effect could also be reversed by blocking the IL-10/STAT3 pathway with Ab9969 and Stattic. In summary, PBMSCs could mediate the polarization of M2 macrophages by activating the IL-10/STAT3 pathway.
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spelling doaj-art-b0a3937e7d95489db00ba3ec9d75fa6b2025-02-03T06:05:48ZengWileyStem Cells International1687-96782022-01-01202210.1155/2022/5181241Peripheral Blood-Derived Mesenchymal Stem Cells Modulate Macrophage Plasticity through the IL-10/STAT3 PathwayQi-Ming Pang0Rui Yang1Meng Zhang2Wang-Hui Zou3Nan-Nan Qian4Qi-Jing Xu5Hui Chen6Jia-Chen Peng7Xiao-Ping Luo8Qian Zhang9Tao Zhang10Key Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine CentreKey Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine CentreKey Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine CentreKey Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine CentreKey Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine CentreDepartment of Human AnatomyKey Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine CentreDepartment of OrthopedicsKey Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine CentreDepartment of Human AnatomyKey Laboratory of Cell Engineering of Guizhou Province and Regenerative Medicine CentreMesenchymal stem cells (MSCs) are multipotent cells that can skew the balance of M1/M2 macrophage polarization towards the M2 phenotype via their paracrine effects, thereby promoting anatomical and functional recovery after many inflammatory diseases induced by macrophages. However, the underlying mechanism is still poorly understood. This study focused on the IL-10/STAT3 pathway and investigated whether IL-10 secreted by PBMSCs could mediate M2 polarization through the activation of this pathway. In this study, a Transwell system was used for coculturing macrophages and PBMSCs. ELISA and RT-qPCR analysis found that PBMSCs and their conditioned media (P-CM) significantly induced the expression of IL-10, while significantly inhibiting the expression of IL-1β and TNF-α; moreover, this effect could be reversed by adding Ab9969 (an IL-10 neutralizing antibody) and Stattic (a STAT3 inhibitor). Furthermore, western blotting and immunofluorescence assays demonstrated that JAK1/STAT3 signaling was significantly upregulated in macrophages cocultured with PBMSCs or P-CM, accompanied by an increase in the M2 biomarker CD206 and a decrease in the M1 biomarker CD86. This effect could also be reversed by blocking the IL-10/STAT3 pathway with Ab9969 and Stattic. In summary, PBMSCs could mediate the polarization of M2 macrophages by activating the IL-10/STAT3 pathway.http://dx.doi.org/10.1155/2022/5181241
spellingShingle Qi-Ming Pang
Rui Yang
Meng Zhang
Wang-Hui Zou
Nan-Nan Qian
Qi-Jing Xu
Hui Chen
Jia-Chen Peng
Xiao-Ping Luo
Qian Zhang
Tao Zhang
Peripheral Blood-Derived Mesenchymal Stem Cells Modulate Macrophage Plasticity through the IL-10/STAT3 Pathway
Stem Cells International
title Peripheral Blood-Derived Mesenchymal Stem Cells Modulate Macrophage Plasticity through the IL-10/STAT3 Pathway
title_full Peripheral Blood-Derived Mesenchymal Stem Cells Modulate Macrophage Plasticity through the IL-10/STAT3 Pathway
title_fullStr Peripheral Blood-Derived Mesenchymal Stem Cells Modulate Macrophage Plasticity through the IL-10/STAT3 Pathway
title_full_unstemmed Peripheral Blood-Derived Mesenchymal Stem Cells Modulate Macrophage Plasticity through the IL-10/STAT3 Pathway
title_short Peripheral Blood-Derived Mesenchymal Stem Cells Modulate Macrophage Plasticity through the IL-10/STAT3 Pathway
title_sort peripheral blood derived mesenchymal stem cells modulate macrophage plasticity through the il 10 stat3 pathway
url http://dx.doi.org/10.1155/2022/5181241
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