title: Chelerythrine ameliorates acute cardiac allograft rejection in mice.
abstract: The improvement in graft survival over the past decade has been mainly due to calcineurin inhibitors, which interfere with the calcium-mediated pathway. Recently, other pathways such as those mediated by protein kinase C (PKC) are coming into view. The purpose of this study was to assess the immunosuppressive properties of chelerythrine, a specific PKC inhibitor, in preventing acute rejection in murine heterotopic heart transplantation. Mice were randomly divided into control and chelerythrine treated group. The control group received PBS while the chelerythrine treated group was given intraperitoneal injection doses (1, 5, 10mg/kg) of chelerythrine from day 0 to day 14 after heart transplantation. Six days after transplantation, cardiac allografts were harvested for further tests. The mean survival time (MST) of the cardiac allograft in untreated animals was 8days while graft MSTs observed in chelerythrine treated group was 13 and 23days at 5 and 10mg/kg treatment doses, respectively (P<0.05). Histologic assessment of the allograft in chelerythrine group showed a significant decline in histologic rejection score, as well as CD4+ and CD8+ T cell infiltration and ICAM-1+ endothelial cell activation. Down-regulation of Th1/Th2 cytokine expression was observed in chelerythrine treatment group. Meanwhile, chelerythrine was also found to inhibit the dephosphorylation of phosphorylated nuclear factor of activated T cells (NFAT) protein 1 and 4.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Zhejiang Province, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China.
authors.forename: Qiyi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Zhejiang Province, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Zhejiang Province, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China.
authors.forename: Jixuan
authors.initials: J
authors.lastname: Duan
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Zhejiang Province, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China.
authors.forename: Jingjin
authors.initials: J
authors.lastname: Wu
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Zhejiang Province, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yan
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Zhejiang Province, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Zhejiang Province, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Meng
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Zhejiang Province, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China.
authors.forename: Kwabena Gyabaah
authors.initials: KG
authors.lastname: Owusu-Ansah
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Zhejiang Province, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, China. Electronic address: zyzss@zju.edu.cn.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000208:Acute Disease; D000818:Animals; D053119:Benzophenanthridines / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D016027:Heart Transplantation; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000276:immunology*; D050778:NFATC Transcription Factors / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D014184:Transplantation, Homologous
chemical_list: D053119:Benzophenanthridines; D016207:Cytokines; D007166:Immunosuppressive Agents; D050778:NFATC Transcription Factors; C494007:Nfatc2 protein, mouse; C494009:Nfatc3 protein, mouse; C016299:chelerythrine; D011493:Protein Kinase C
keywords: Chelerythrine; Heart transplantation; Mice; NFAT; PKC inhibitor