title: Sphingosine-1-phosphate receptor 1 agonist SEW2871 prolongs heterotopic heart allograft survival in mice.
abstract: Sphingosine-1-phosphate (S1P) is a biologically active metabolite of plasma-membrane sphingolipids that is essential for immune cell trafficking. Recent studies have revealed immunomodulatory functions of S1P and its receptors (S1PR1-S1PR5) in many inflammatory conditions, such as asthma and autoimmunity. Here, we explore the efficacy of SEW2871, a selective S1PR1 agonist, in the prevention of acute allograft rejection in a murine cardiac transplantation model. Treatment of recipient mice with SEW2871 significantly prolongs cardiac allograft survival as compared to those recipients treated with control vehicle. The enhanced graft survival is associated with reduced circulating lymphocytes and allograft inflammatory cell infiltration. The cytokine analysis showed decreased allograft expression of TNF-α, IFN-γ and IL-2 in the SEW2871-treated mice. Moreover, administration of SEW2871 increases the percentage of CD4(+) T regulatory cells and FoxP3 expression in spleen of allograft recipients. Therefore, SEW2871 plays a critical role in regulation of lymphocyte trafficking and development, which directly contributes to prolongation of the allograft survival.
authors.affiliation: Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ni
authors.affiliation: Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Baohong
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lan
authors.affiliation: Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.affiliation: Intensive Care Unit, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China.
authors.forename: Liangcheng
authors.initials: L
authors.lastname: Dai
authors.affiliation: Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xiaobao
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Microbiology and Immunology, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: huiyin0103@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Yin
mesh_terms: D000818:Animals; D003627:Data Interpretation, Statistical; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D016027:Heart Transplantation; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010069:Oxadiazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D000081025:Sphingosine-1-Phosphate Receptors; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016042:Transplantation, Heterotopic
chemical_list: D010069:Oxadiazoles; D049349:Receptors, Lysosphingolipid; C556330:S1pr1 protein, mouse; C503964:SEW2871; D000081025:Sphingosine-1-Phosphate Receptors; D013876:Thiophenes
keywords: Cardiac allograft; Cytokine; Lymphocyte; SEW2871; Sphingosine-1-phosphate receptor 1