title: Amelioration of myocarditis by statin through inhibiting cross-talk between antigen presenting cells and lymphocytes in rats.
abstract: Statins, inhibitors of 3-hydroxy-3-methylglutary-coenzyme A (HMG-CoA) reductase, have been recognized as a new type of immunomodulator and reported to have anti-inflammatory effect. To investigate the effect of simvastatin, a lipophilic statin, on myocarditis, we explored whether simvastatin is able to inhibit experimental autoimmune myocarditis (EAM) and adoptive transfer of EAM in rats. We found that administration of simvastatin not only interfered with the development of EAM, but also inhibited the transfer. Antigen presenting cells (APCs) were proved to be important for the development of EAM. The ability of myocarditic splenocytes to transfer myocarditis was enhanced after co-culture with APCs. During co-culture of the myocarditic splenocytes and the APCs, simvastatin not only decreased percentages of CD28 expression in CD4-positive myocarditic splenocytes, and CD80 and CD86 expressions in APCs, but also inhibited the production of tumor necrosis factor (TNF)-partial differential in the CD4-positive myocarditic splenocytes and the APCs. These results indicate that simvastatin was able to ameliorate EAM through the inhibition of cross-talk between lymphocytes and APCs, suggesting beneficial role of simvastatin in the treatment of autoimmune myocarditis.
authors.affiliation: Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan; Department of Cardiology, First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Jia-Lu
authors.initials: JL
authors.lastname: Wu
authors.affiliation: Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Matsui
authors.affiliation: Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan. Electronic address: zong3961@kanazawa-med.ac.jp.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Zong
authors.affiliation: Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Katsuzo
authors.initials: K
authors.lastname: Nishikawa
authors.affiliation: Department of Cardiology, First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Bao-Gui
authors.initials: BG
authors.lastname: Sun
authors.affiliation: Department of Pathology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Katsuda
authors.affiliation: Wallenberg Laboratory c/o Department of Medicine, Sahlgrenska University Hospital, University of Göteborg, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Fu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002450:Cell Communication / Q000187:drug effects* / Q000276:immunology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009205:Myocarditis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D013154:Spleen / Q000276:immunology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin