title: Upregulation of the apoptosis-related inflammasome in cardiac allograft rejection.
abstract: BACKGROUND
  Inflammation is a major factor in cardiac allograft rejection. Accumulating reports have demonstrated an important role of the inflammation-induced adaptor complex, called the inflammasome, in the field of immunology. The apoptosis-associated, speck-like protein containing a caspase recruitment domain (ASC) is an adaptor protein that forms the inflammasome and regulates caspase-1-dependent generation of inflammatory cytokines. The aim of the present study was to determine how ASC is associated with the development of cardiac allograft rejection.
  
  
  METHODS
  We used a murine heterotopic cardiac transplantation model between fully incompatible strains. Donor hearts (n = 9 for each time-point) were harvested for examination on Days 1, 4, 7 and 12 after transplantation. Histopathologic findings of cardiac grafts were evaluated using rejection scores. The expression of ASC and inflammatory cytokines in cardiac grafts were analyzed by immunohistochemistry and real-time reverse transcript-polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Expression levels of both ASC and IL-1 beta were higher in the myocardial interstitium of allografts in parallel to the progress of cardiac rejection during the acute phase after transplantation. In contrast, expression of ASC and IL-1 beta remained low in isografts. Cardiac allografts treated with tacrolimus showed decreased expression of both ASC and IL-1 beta similar to that seen in isografts. Real-time RT-PCR demonstrated similar alteration of ASC and IL-1 beta mRNA expression in cardiac grafts during the acute phase.
  
  
  CONCLUSIONS
  Our results demonstrate a novel finding showing that upregulation of ASC is closely associated with the inflammation induced in cardiac grafts after transplantation in the mouse.
authors.affiliation: Department of Surgery (II), School of Medicine, Shinshu University, Matsumoto, Japan.
authors.forename: Tatsuichiro
authors.initials: T
authors.lastname: Seto
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kamijo
authors.forename: Yuko
authors.initials: Y
authors.lastname: Wada
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamaura
authors.forename: Kohei
authors.initials: K
authors.lastname: Takahashi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Komatsu
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Otsu
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Terasaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fukui
authors.forename: Jun
authors.initials: J
authors.lastname: Amano
authors.forename: Shun'ichiro
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Junji
authors.initials: J
authors.lastname: Sagara
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ito
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D016027:Heart Transplantation / Q000473:pathology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D014184:Transplantation, Homologous; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D053583:Interleukin-1beta; C498534:Pycard protein, mouse; D012333:RNA, Messenger