Upregulation of the apoptosis-related inflammasome in cardiac allograft rejection.
J Heart Lung Transplant
; 29(3): 352-9, 2010 Mar.
Article
in En
| MEDLINE
| ID: mdl-20036165
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Up-Regulation
/
Heart Transplantation
/
Cytoskeletal Proteins
/
Graft Rejection
/
Inflammation
/
Myocardium
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Heart Lung Transplant
Journal subject:
CARDIOLOGIA
/
TRANSPLANTE
Year:
2010
Document type:
Article
Affiliation country:
Japan