Artesunate Restrains Maturation of Dendritic Cells and Ameliorates Heart Transplantation-Induced Acute Rejection in Mice through the PERK/ATF4/CHOP Signaling Pathway
Background. Heart transplantation (HT) is the only effective treatment for end-stage heart failure because it can effectively improve the survival rate and quality of life of patients with heart failure. Artesunate (ART) is an artemisinin derivative, with good water solubility and higher oral bioava...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/2481907 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832546067727515648 |
|---|---|
| author | Yuanyang Chen Sihao Zheng Zhiwei Wang Xin Cai Yanjia Che Qi Wu Shun Yuan Xiaohan Zhong |
| author_facet | Yuanyang Chen Sihao Zheng Zhiwei Wang Xin Cai Yanjia Che Qi Wu Shun Yuan Xiaohan Zhong |
| author_sort | Yuanyang Chen |
| collection | DOAJ |
| description | Background. Heart transplantation (HT) is the only effective treatment for end-stage heart failure because it can effectively improve the survival rate and quality of life of patients with heart failure. Artesunate (ART) is an artemisinin derivative, with good water solubility and higher oral bioavailability. The main aim of this study was to determine the role of ART in HT mice. Methods. In animal experiments, mice were divided into the control group, HT group, low ART+HT group, and high ART+HT group. Next, inflammatory cell infiltration, oxidative stress injury, and myocardial cell apoptosis were determined in heart tissue. The proportion of multiple lymphocytes in spleen and lymph nodes was then determined using flow cytometry. In addition, cell experiments were conducted to determine the changes in expression of surface maturation markers of BMDC and changes in intracellular reactive oxygen species after LPS stimulation. Finally, western blot analysis was performed to determine the levels of endoplasmic reticulum stress-related proteins (CHOP/ATF4/PERK). Results. The survival time of mice in the ART treatment group was significantly prolonged and was positively correlated with the dose. In animal experiments, ART significantly reduced inflammatory cell infiltration in heart tissue and the proportion of CD4+CD8+ T cells in spleens and lymph nodes. Moreover, ART treatment lowered the 8-OHdg in hearts and myocardial apoptosis. In cell experiments, ART treatment slowed down the development and maturation of BMDCs by inhibiting the expression of endoplasmic reticulum stress-related proteins. Furthermore, the treatment alleviated the oxidative stress damage of BMDCs. Conclusion. ART can inhibit maturation of dendritic cells through the endoplasmic reticulum stress signaling pathway, thereby alleviating acute rejection in mice after heart transplantation. |
| format | Article |
| id | doaj-art-83662bf8af4d4e1b8f4bff8432610dc9 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-83662bf8af4d4e1b8f4bff8432610dc92025-02-03T07:23:57ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/24819072481907Artesunate Restrains Maturation of Dendritic Cells and Ameliorates Heart Transplantation-Induced Acute Rejection in Mice through the PERK/ATF4/CHOP Signaling PathwayYuanyang Chen0Sihao Zheng1Zhiwei Wang2Xin Cai3Yanjia Che4Qi Wu5Shun Yuan6Xiaohan Zhong7Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, 430060 Hubei, ChinaDepartment of Cardiovascular Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, 430060 Hubei, ChinaDepartment of Cardiovascular Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, 430060 Hubei, ChinaDepartment of Cardiovascular Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, 430060 Hubei, ChinaDepartment of Cardiovascular Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, 430060 Hubei, ChinaDepartment of Cardiovascular Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, 430060 Hubei, ChinaDepartment of Cardiovascular Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, 430060 Hubei, ChinaDepartment of Cardiovascular Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, 430060 Hubei, ChinaBackground. Heart transplantation (HT) is the only effective treatment for end-stage heart failure because it can effectively improve the survival rate and quality of life of patients with heart failure. Artesunate (ART) is an artemisinin derivative, with good water solubility and higher oral bioavailability. The main aim of this study was to determine the role of ART in HT mice. Methods. In animal experiments, mice were divided into the control group, HT group, low ART+HT group, and high ART+HT group. Next, inflammatory cell infiltration, oxidative stress injury, and myocardial cell apoptosis were determined in heart tissue. The proportion of multiple lymphocytes in spleen and lymph nodes was then determined using flow cytometry. In addition, cell experiments were conducted to determine the changes in expression of surface maturation markers of BMDC and changes in intracellular reactive oxygen species after LPS stimulation. Finally, western blot analysis was performed to determine the levels of endoplasmic reticulum stress-related proteins (CHOP/ATF4/PERK). Results. The survival time of mice in the ART treatment group was significantly prolonged and was positively correlated with the dose. In animal experiments, ART significantly reduced inflammatory cell infiltration in heart tissue and the proportion of CD4+CD8+ T cells in spleens and lymph nodes. Moreover, ART treatment lowered the 8-OHdg in hearts and myocardial apoptosis. In cell experiments, ART treatment slowed down the development and maturation of BMDCs by inhibiting the expression of endoplasmic reticulum stress-related proteins. Furthermore, the treatment alleviated the oxidative stress damage of BMDCs. Conclusion. ART can inhibit maturation of dendritic cells through the endoplasmic reticulum stress signaling pathway, thereby alleviating acute rejection in mice after heart transplantation.http://dx.doi.org/10.1155/2021/2481907 |
| spellingShingle | Yuanyang Chen Sihao Zheng Zhiwei Wang Xin Cai Yanjia Che Qi Wu Shun Yuan Xiaohan Zhong Artesunate Restrains Maturation of Dendritic Cells and Ameliorates Heart Transplantation-Induced Acute Rejection in Mice through the PERK/ATF4/CHOP Signaling Pathway Mediators of Inflammation |
| title | Artesunate Restrains Maturation of Dendritic Cells and Ameliorates Heart Transplantation-Induced Acute Rejection in Mice through the PERK/ATF4/CHOP Signaling Pathway |
| title_full | Artesunate Restrains Maturation of Dendritic Cells and Ameliorates Heart Transplantation-Induced Acute Rejection in Mice through the PERK/ATF4/CHOP Signaling Pathway |
| title_fullStr | Artesunate Restrains Maturation of Dendritic Cells and Ameliorates Heart Transplantation-Induced Acute Rejection in Mice through the PERK/ATF4/CHOP Signaling Pathway |
| title_full_unstemmed | Artesunate Restrains Maturation of Dendritic Cells and Ameliorates Heart Transplantation-Induced Acute Rejection in Mice through the PERK/ATF4/CHOP Signaling Pathway |
| title_short | Artesunate Restrains Maturation of Dendritic Cells and Ameliorates Heart Transplantation-Induced Acute Rejection in Mice through the PERK/ATF4/CHOP Signaling Pathway |
| title_sort | artesunate restrains maturation of dendritic cells and ameliorates heart transplantation induced acute rejection in mice through the perk atf4 chop signaling pathway |
| url | http://dx.doi.org/10.1155/2021/2481907 |
| work_keys_str_mv | AT yuanyangchen artesunaterestrainsmaturationofdendriticcellsandameliorateshearttransplantationinducedacuterejectioninmicethroughtheperkatf4chopsignalingpathway AT sihaozheng artesunaterestrainsmaturationofdendriticcellsandameliorateshearttransplantationinducedacuterejectioninmicethroughtheperkatf4chopsignalingpathway AT zhiweiwang artesunaterestrainsmaturationofdendriticcellsandameliorateshearttransplantationinducedacuterejectioninmicethroughtheperkatf4chopsignalingpathway AT xincai artesunaterestrainsmaturationofdendriticcellsandameliorateshearttransplantationinducedacuterejectioninmicethroughtheperkatf4chopsignalingpathway AT yanjiache artesunaterestrainsmaturationofdendriticcellsandameliorateshearttransplantationinducedacuterejectioninmicethroughtheperkatf4chopsignalingpathway AT qiwu artesunaterestrainsmaturationofdendriticcellsandameliorateshearttransplantationinducedacuterejectioninmicethroughtheperkatf4chopsignalingpathway AT shunyuan artesunaterestrainsmaturationofdendriticcellsandameliorateshearttransplantationinducedacuterejectioninmicethroughtheperkatf4chopsignalingpathway AT xiaohanzhong artesunaterestrainsmaturationofdendriticcellsandameliorateshearttransplantationinducedacuterejectioninmicethroughtheperkatf4chopsignalingpathway |