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Aspirin Attenuates Cardiac Allograft Rejection by Inhibiting the Maturation of Dendritic Cells via the NF-κB Signaling Pathway

Background: Dendritic cells (DCs) serve as an important part of the immune system and play a dual role in immune response. Mature DCs can initiate immune response, while immature or semi-mature DCs induce immune hyporesponsiveness or tolerance. Previous studies have shown that aspirin can effectivel...

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Autores principales: Zhang, Xi, Chang, Aie, Zou, Yanqiang, Xu, Heng, Cui, Jikai, Chen, Zhang, Li, Yuan, Du, Yifan, Wu, Jie, Yu, Jizhang, Du, Xinling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415307/
https://www.ncbi.nlm.nih.gov/pubmed/34483913
http://dx.doi.org/10.3389/fphar.2021.706748
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author Zhang, Xi
Chang, Aie
Zou, Yanqiang
Xu, Heng
Cui, Jikai
Chen, Zhang
Li, Yuan
Du, Yifan
Wu, Jie
Yu, Jizhang
Du, Xinling
author_facet Zhang, Xi
Chang, Aie
Zou, Yanqiang
Xu, Heng
Cui, Jikai
Chen, Zhang
Li, Yuan
Du, Yifan
Wu, Jie
Yu, Jizhang
Du, Xinling
author_sort Zhang, Xi
collection PubMed
description Background: Dendritic cells (DCs) serve as an important part of the immune system and play a dual role in immune response. Mature DCs can initiate immune response, while immature or semi-mature DCs induce immune hyporesponsiveness or tolerance. Previous studies have shown that aspirin can effectively inhibit the maturation of DCs. However, the protective effect of aspirin on acute cardiac allograft rejection has not been studied. The aim of this study was to elucidate the effect of aspirin exert on allograft rejection. Methods: The model of MHC-mismatched (BALB/c to B6 mice) heterotopic heart transplantation was established and administered intraperitoneal injection with aspirin. The severity of allograft rejection, transcriptional levels of cytokines, and characteristics of immune cells were assessed. Bone marrow-derived dendritic cells (BMDCs) were generated with or without aspirin. The function of DCs was determined via mixed lymphocyte reaction (MLR). The signaling pathway of DCs was detected by Western blotting. Results: Aspirin significantly prolonged the survival of cardiac allograft in mouse, inhibited the production of pro-inflammatory cytokines and the differentiation of effector T cells (Th1 and Th17), as well as promoted the regulatory T cells (Treg). The maturation of DCs in the spleen was obviously suppressed with aspirin treatment. In vitro, aspirin decreased the activation of NF-κB signaling of DCs, as well as impeded MHCII and co-stimulatory molecules (CD80, CD86, and CD40) expression on DCs. Moreover, both the pro-inflammatory cytokines and function of DCs were suppressed by aspirin. Conclusion: Aspirin inhibits the maturation of DCs through the NF-κB signaling pathway and attenuates acute cardiac allograft rejection.
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spelling pubmed-84153072021-09-04 Aspirin Attenuates Cardiac Allograft Rejection by Inhibiting the Maturation of Dendritic Cells via the NF-κB Signaling Pathway Zhang, Xi Chang, Aie Zou, Yanqiang Xu, Heng Cui, Jikai Chen, Zhang Li, Yuan Du, Yifan Wu, Jie Yu, Jizhang Du, Xinling Front Pharmacol Pharmacology Background: Dendritic cells (DCs) serve as an important part of the immune system and play a dual role in immune response. Mature DCs can initiate immune response, while immature or semi-mature DCs induce immune hyporesponsiveness or tolerance. Previous studies have shown that aspirin can effectively inhibit the maturation of DCs. However, the protective effect of aspirin on acute cardiac allograft rejection has not been studied. The aim of this study was to elucidate the effect of aspirin exert on allograft rejection. Methods: The model of MHC-mismatched (BALB/c to B6 mice) heterotopic heart transplantation was established and administered intraperitoneal injection with aspirin. The severity of allograft rejection, transcriptional levels of cytokines, and characteristics of immune cells were assessed. Bone marrow-derived dendritic cells (BMDCs) were generated with or without aspirin. The function of DCs was determined via mixed lymphocyte reaction (MLR). The signaling pathway of DCs was detected by Western blotting. Results: Aspirin significantly prolonged the survival of cardiac allograft in mouse, inhibited the production of pro-inflammatory cytokines and the differentiation of effector T cells (Th1 and Th17), as well as promoted the regulatory T cells (Treg). The maturation of DCs in the spleen was obviously suppressed with aspirin treatment. In vitro, aspirin decreased the activation of NF-κB signaling of DCs, as well as impeded MHCII and co-stimulatory molecules (CD80, CD86, and CD40) expression on DCs. Moreover, both the pro-inflammatory cytokines and function of DCs were suppressed by aspirin. Conclusion: Aspirin inhibits the maturation of DCs through the NF-κB signaling pathway and attenuates acute cardiac allograft rejection. Frontiers Media S.A. 2021-08-16 /pmc/articles/PMC8415307/ /pubmed/34483913 http://dx.doi.org/10.3389/fphar.2021.706748 Text en Copyright © 2021 Zhang, Chang, Zou, Xu, Cui, Chen, Li, Du, Wu, Yu and Du. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhang, Xi
Chang, Aie
Zou, Yanqiang
Xu, Heng
Cui, Jikai
Chen, Zhang
Li, Yuan
Du, Yifan
Wu, Jie
Yu, Jizhang
Du, Xinling
Aspirin Attenuates Cardiac Allograft Rejection by Inhibiting the Maturation of Dendritic Cells via the NF-κB Signaling Pathway
title Aspirin Attenuates Cardiac Allograft Rejection by Inhibiting the Maturation of Dendritic Cells via the NF-κB Signaling Pathway
title_full Aspirin Attenuates Cardiac Allograft Rejection by Inhibiting the Maturation of Dendritic Cells via the NF-κB Signaling Pathway
title_fullStr Aspirin Attenuates Cardiac Allograft Rejection by Inhibiting the Maturation of Dendritic Cells via the NF-κB Signaling Pathway
title_full_unstemmed Aspirin Attenuates Cardiac Allograft Rejection by Inhibiting the Maturation of Dendritic Cells via the NF-κB Signaling Pathway
title_short Aspirin Attenuates Cardiac Allograft Rejection by Inhibiting the Maturation of Dendritic Cells via the NF-κB Signaling Pathway
title_sort aspirin attenuates cardiac allograft rejection by inhibiting the maturation of dendritic cells via the nf-κb signaling pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415307/
https://www.ncbi.nlm.nih.gov/pubmed/34483913
http://dx.doi.org/10.3389/fphar.2021.706748
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