title: Astilbin suppresses acute heart allograft rejection by inhibiting maturation and function of dendritic cells in mice.
abstract: The effect of astilbin on acute graft rejection was investigated in C57BL/6 mice carrying BALB/c hearts heterotopically transplanted into the neck vessels. Daily treatment with astilbin (50, 125, or 250 mg/kg intraperitoneally) significantly prolonged the survival of grafts in a dose-dependent manner, when cyclosporine (CsA; 5 mg/kg) was co-administered with astilbin (250 mg/kg), there was more potent immunosuppression than that solely achieved by 20 mg/kg CsA. Addition of 10 mg/mL astilbin significantly inhibited the proliferation and activation of T cells, as determined by (3)H-thymidine deoxyribose uptake, Western blots for nuclear factor κB and p38, and 1-way mixed lymphocyte reactions (MLR). Mature and antigen-presenting functions of dendritic cells (DCs) also were inhibited by astilbin (10 mg/mL), as determined by morphologic observations, flow cytometry, and MLR. These observations suggested that astilbin is a potential candidate for immunosuppressive therapy after heart engraftment. Inhibiting the maturation and antigen-presenting function of DCs and thus preventing T-cells activation is a possible mechanism underlying its inhibitory effects on acute heart allograft rejection.
authors.affiliation: General Surgery Department, Shanghai Jiao Tong University Sixth People's Hospital, Shanghai, China.
authors.forename: S
authors.initials: S
authors.lastname: Zou
authors.forename: X
authors.initials: X
authors.lastname: Shen
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.forename: Z
authors.initials: Z
authors.lastname: Fu
authors.forename: Q
authors.initials: Q
authors.lastname: Zheng
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D044948:Flavonols / Q000008:administration & dosage / Q000494:pharmacology*; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D044948:Flavonols; D007166:Immunosuppressive Agents; C099069:astilbin; D016572:Cyclosporine