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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2006-3-16
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pubmed:abstractText |
This study was undertaken to determine if PG490-88 and tacrolimus (Tac) act synergistically to prevent renal allograft rejection in monkeys and to explore possible mechanisms of synergy between these agents. MHC-mismatched renal allografts were transplanted into cynomolgus monkeys after bilateral nephrectomy. Recipients were divided into the following groups: (i) no treatment; (ii) PG490-88 (0.03 mg/kg); (iii) Tac (1 mg/kg); (iv) PG490-88 (0.01 mg/kg) + Tac (1 mg/kg) and (v) PG490-88 (0.03 mg/kg) + Tac (1 mg/kg). Through synergy PG490-88 and Tac inhibited anti-CD3/PMA-induced T-cell proliferation and IFN-gamma expression in vitro. Tac monotherapy only marginally prolonged survival (27 +/- 3.2 days), while the combination of PG490-88 and Tac significantly prolonged graft survival to a median of 99 days (PG490-88 at 0.03 mg) and 38.5 days (PG490-88 at 0.01 mg/kg). Prolonged survival correlated with inhibited IgM production as well as reduced T-cell infiltration, IL-2 protein expression and NF-AT/NF-kappaB activity. We conclude that PG490-88 and a subtherapeutic dose of Tac significantly prolong renal allograft survival in monkeys through the synergistic inhibition of T-cell activation and a decrease in IFN-gamma production and NF-AT/NF-kappaB activity.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1600-6135
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pubmed:author |
pubmed-author:ArnHH,
pubmed-author:ChenGG,
pubmed-author:FangZZ,
pubmed-author:GarciaBB,
pubmed-author:HuangXX,
pubmed-author:LiuWW,
pubmed-author:MadenasJJ,
pubmed-author:MadrenasJJ,
pubmed-author:RamcharranSS,
pubmed-author:SudoYY,
pubmed-author:SuhBB,
pubmed-author:TamuraKK,
pubmed-author:WangXX,
pubmed-author:WissOO,
pubmed-author:XiangYY,
pubmed-author:YangHH,
pubmed-author:ZhongRR
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pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
714-23
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16539628-Animals,
pubmed-meshheading:16539628-Cell Proliferation,
pubmed-meshheading:16539628-Diterpenes,
pubmed-meshheading:16539628-Drug Synergism,
pubmed-meshheading:16539628-Graft Rejection,
pubmed-meshheading:16539628-Graft Survival,
pubmed-meshheading:16539628-Haplorhini,
pubmed-meshheading:16539628-Immunoglobulin M,
pubmed-meshheading:16539628-Immunosuppressive Agents,
pubmed-meshheading:16539628-Interferon-gamma,
pubmed-meshheading:16539628-Interleukin-2,
pubmed-meshheading:16539628-Kidney Transplantation,
pubmed-meshheading:16539628-Male,
pubmed-meshheading:16539628-NF-kappa B,
pubmed-meshheading:16539628-NFATC Transcription Factors,
pubmed-meshheading:16539628-T-Lymphocytes,
pubmed-meshheading:16539628-Tacrolimus,
pubmed-meshheading:16539628-Transcriptional Activation
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pubmed:year |
2006
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pubmed:articleTitle |
A synergistic effect between PG490-88 and tacrolimus prolongs renal allograft survival in monkeys.
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pubmed:affiliation |
Department of Surgery, The University of Western Ontario, London, Ontario, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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