Survival of mitomycin C-treated pancreatic islet xenografts is mediated by increased expression of transforming growth factor-beta.
Transplantation
; 77(6): 907-14, 2004 Mar 27.
Article
en En
| MEDLINE
| ID: mdl-15077036
ABSTRACT
BACKGROUND:
Mitomycin C (MMC) can trigger various intracellular signals. The authors previously showed that pretreatment of highly immunogenic crude pancreatic islets with MMC improved their survival in a rat-to-mouse transplantation model. The aim of this study was to investigate the role of transforming growth factor (TGF)-beta in mediating MMC-induced survival of islet xenografts.METHODS:
Collagenase-digested islets obtained from WS rats (RT1k) were incubated for 30 min with 10 microg/mL MMC and then transplanted into streptozotocin-induced diabetic C57BL/6 (H-2b) mice after 20 hr of culture at 37 degrees C.RESULTS:
Survival of xenografts was enhanced by pretreatment of islets with MMC. MMC-treated xenografts showed a mild inflammatory cell response and significantly minimal infiltration of macrophages, CD4 T cells, and CD8 T cells compared with untreated grafts. TGF-beta mRNA was increased at 20 hr after MMC treatment, and TGF-beta protein expression was also increased compared with untreated islet xenografts. TGF-beta concentration in blebs formed around the xenografts (but not in the serum) was higher in animals that underwent transplantation with MMC-treated islets than with untreated islets. Simultaneous transplantation of MMC-treated and untreated islets separately in each kidney of recipient mice showed that protection was only found in MMC-treated islets. Treatment of islets before transplantation by neutralizing anti-TGF-beta antibody suppressed the MMC-protective effects on graft survival, whereas no such effect was noted with isotype-matched immunoglobulin.CONCLUSIONS:
The authors' results indicate that MMC treatment effectively reduces local inflammatory response and that such effects are mediated by increase of TGF-beta during the early period of islet transplantation.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trasplante Heterólogo
/
Trasplante de Islotes Pancreáticos
/
Factor de Crecimiento Transformador beta
/
Mitomicina
/
Supervivencia de Injerto
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Transplantation
Año:
2004
Tipo del documento:
Article
País de afiliación:
Japón