Document Detail

Activation of Peroxisome Proliferator-activated Receptor γ Prolongs Islet Allograft Survival.
MedLine Citation:
PMID:  22469179     Owner:  NLM     Status:  Publisher    
Exposing donor mice to carbon monoxide (CO) protects transplanted islet allografts from immune rejection after transplantation (referred as the "donor" effect). In an attempt to understand the mechanisms of the donor effect of CO, we found that donor treatment with CO upregulates expression of peroxisome proliferator-activated receptor gamma (PPARγ), a transcriptional regulator, in isolated islets. In this study, we evaluated whether PPARγ contributes to the survival and function of transplanted islets and whether PPARγ mediates the protective effect of CO in a major mismatch islet allogeneic transplantation model.BALB/c (H-2(d)) islets in which PPARγ activity was induced by its agonists, 15- deoxy-Δ(12-14)-prostaglandin J2 (15d-PGJ2) or troglitazone were transplanted into C57BL/6 (H-2(b)) recipients that had been rendered diabetic by streptozotocin (STZ). Blood glucose levels of recipients were monitored to determine the function of transplanted islets. Our data indicated that PPARγ activation in islets led to a high percentage of BALB/c islets survived long-term in C57BL/6 recipients. Activation of PPARγ in the donor suppresses expressions of proinflammatory cytokines including tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) in transplanted islets. Blocking PPARγ activity by its antagonist, GW9662, abrogated the donor effect of CO in vivo and in vitro. Our data demonstrate that PPARγ plays a critical role in the survival and function of transplanted islets after transplantation in the recipient. The protective effects of CO are at least in part mediated by PPARγ.
Hongjun Wang; Hongju Wu; Fredy Rocuts; Zhuoying Gu; Fritz H Bach; Leo E Otterbein
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-28
Journal Detail:
Title:  Cell transplantation     Volume:  -     ISSN:  1555-3892     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-4-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9208854     Medline TA:  Cell Transplant     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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