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

Xi Zhang; Aie Chang; Yanqiang Zou; Heng Xu; Jikai Cui; Zhang Chen; Yuan Li; Yifan Du; Jie Wu; Jizhang Yu; Xinling Du

doi:10.3389/fphar.2021.706748

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

Front Pharmacol. 2021 Aug 16:12:706748. doi: 10.3389/fphar.2021.706748. eCollection 2021.

Authors

Xi Zhang¹, Aie Chang², Yanqiang Zou¹, Heng Xu¹, Jikai Cui¹, Zhang Chen¹, Yuan Li¹, Yifan Du¹, Jie Wu¹, Jizhang Yu¹, Xinling Du¹

Affiliations

¹ Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

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.

Keywords: NF-κB; allograft rejection; aspirin; dendritic cells; heart transplantation.