PMID- 34483913 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210907 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 12 DP - 2021 TI - Aspirin Attenuates Cardiac Allograft Rejection by Inhibiting the Maturation of Dendritic Cells via the NF-kappaB Signaling Pathway. PG - 706748 LID - 10.3389/fphar.2021.706748 [doi] LID - 706748 AB - 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-kappaB 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-kappaB signaling pathway and attenuates acute cardiac allograft rejection. CI - Copyright (c) 2021 Zhang, Chang, Zou, Xu, Cui, Chen, Li, Du, Wu, Yu and Du. FAU - Zhang, Xi AU - Zhang X AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Chang, Aie AU - Chang A AD - Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zou, Yanqiang AU - Zou Y AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Xu, Heng AU - Xu H AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Cui, Jikai AU - Cui J AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Chen, Zhang AU - Chen Z AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Li, Yuan AU - Li Y AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Du, Yifan AU - Du Y AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Wu, Jie AU - Wu J AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Yu, Jizhang AU - Yu J AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Du, Xinling AU - Du X AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. LA - eng PT - Journal Article DEP - 20210816 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8415307 OTO - NOTNLM OT - NF-kappaB OT - allograft rejection OT - aspirin OT - dendritic cells OT - heart transplantation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/09/07 06:00 MHDA- 2021/09/07 06:01 PMCR- 2021/08/16 CRDT- 2021/09/06 05:54 PHST- 2021/05/08 00:00 [received] PHST- 2021/07/05 00:00 [accepted] PHST- 2021/09/06 05:54 [entrez] PHST- 2021/09/07 06:00 [pubmed] PHST- 2021/09/07 06:01 [medline] PHST- 2021/08/16 00:00 [pmc-release] AID - 706748 [pii] AID - 10.3389/fphar.2021.706748 [doi] PST - epublish SO - Front Pharmacol. 2021 Aug 16;12:706748. doi: 10.3389/fphar.2021.706748. eCollection 2021.