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Article: Combined treatment with triptolide and rapamycin prolongs graft survival in a mouse model of cardiac transplantation

TitleCombined treatment with triptolide and rapamycin prolongs graft survival in a mouse model of cardiac transplantation
Authors
KeywordsCardiac allografts
CD4+CD25+Foxp3+ T cells
DC-SIGN
Rapamycin
Th1/Th2 cytokines
Triptolide
Issue Date2008
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journal.asp?ref=0934-0874&site=1
Citation
Transplant International, 2008, v. 21 n. 5, p. 483-494 How to Cite?
AbstractCurrent immunosuppressive strategies for transplantation have failed to achieve long-term graft survival. In this study, we investigate the effects of combined treatment with triptolide (TPT) and rapamycin (Rapa) on graft survival as well as changes in pathology and immunological responses. Heterotopic heart transplantation was performed. TPT and Rapa were administered either alone or in combination. The mean survival time (MST) for the cardiac allografts in animals receiving the combination of TPT and Rapa was 93.5 ± 6.7 days compared to treatment with TPT (MST: 23.5 ± 5.3 days), Rapa (22 ± 1.3 days) alone or no treatment (7.66 ± 0.8 days). Histopathological evaluation showed that inflammatory cell infiltration was markedly reduced in grafts with combined treatment groups. Down-regulation of CCL19, CCR5, CCR7, interferon γ and interleukin (IL)-12 in the combination treatment was accompanied by increased expression of IL-4, IL-10 and CD4+CD25 +Foxp3+ regulatory T (Tr) cells in spleen. Finally, dendritic cell (DC) maturation was impaired by treatment with TPT/Rapa. Our results demonstrate that combination therapy with TPT and Rapa markedly prolongs cardiac allograft survival. This effect is accompanied by inhibition of DCs maturation, conditioning DCs to adopt tolerogenic phenotype, and the expansion of Tr cells. These results add weight to the application of combination therapy in transplantation. © 2008 The Authors.
Persistent Identifierhttp://hdl.handle.net/10722/84575
ISSN
2015 Impact Factor: 2.835
2015 SCImago Journal Rankings: 1.107
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorChen, Yen_HK
dc.contributor.authorLiu, FQen_HK
dc.contributor.authorLamb, JRen_HK
dc.contributor.authorTam, PKHen_HK
dc.date.accessioned2010-09-06T08:54:34Z-
dc.date.available2010-09-06T08:54:34Z-
dc.date.issued2008en_HK
dc.identifier.citationTransplant International, 2008, v. 21 n. 5, p. 483-494en_HK
dc.identifier.issn0934-0874en_HK
dc.identifier.urihttp://hdl.handle.net/10722/84575-
dc.description.abstractCurrent immunosuppressive strategies for transplantation have failed to achieve long-term graft survival. In this study, we investigate the effects of combined treatment with triptolide (TPT) and rapamycin (Rapa) on graft survival as well as changes in pathology and immunological responses. Heterotopic heart transplantation was performed. TPT and Rapa were administered either alone or in combination. The mean survival time (MST) for the cardiac allografts in animals receiving the combination of TPT and Rapa was 93.5 ± 6.7 days compared to treatment with TPT (MST: 23.5 ± 5.3 days), Rapa (22 ± 1.3 days) alone or no treatment (7.66 ± 0.8 days). Histopathological evaluation showed that inflammatory cell infiltration was markedly reduced in grafts with combined treatment groups. Down-regulation of CCL19, CCR5, CCR7, interferon γ and interleukin (IL)-12 in the combination treatment was accompanied by increased expression of IL-4, IL-10 and CD4+CD25 +Foxp3+ regulatory T (Tr) cells in spleen. Finally, dendritic cell (DC) maturation was impaired by treatment with TPT/Rapa. Our results demonstrate that combination therapy with TPT and Rapa markedly prolongs cardiac allograft survival. This effect is accompanied by inhibition of DCs maturation, conditioning DCs to adopt tolerogenic phenotype, and the expansion of Tr cells. These results add weight to the application of combination therapy in transplantation. © 2008 The Authors.en_HK
dc.languageengen_HK
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journal.asp?ref=0934-0874&site=1en_HK
dc.relation.ispartofTransplant Internationalen_HK
dc.rightsTransplant International. Copyright © Blackwell Publishing Ltd.en_HK
dc.rightsThe definitive version is available at www.blackwell-synergy.com-
dc.subjectCardiac allograftsen_HK
dc.subjectCD4+CD25+Foxp3+ T cellsen_HK
dc.subjectDC-SIGNen_HK
dc.subjectRapamycinen_HK
dc.subjectTh1/Th2 cytokinesen_HK
dc.subjectTriptolideen_HK
dc.subject.meshDiterpenes - pharmacology-
dc.subject.meshGraft Survival - drug effects-
dc.subject.meshHeart Transplantation-
dc.subject.meshImmunosuppressive Agents - pharmacology-
dc.subject.meshPhenanthrenes - pharmacology-
dc.titleCombined treatment with triptolide and rapamycin prolongs graft survival in a mouse model of cardiac transplantationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0934-0874&volume=21&issue=5&spage=483&epage=494&date=2008&atitle=Combined+treatment+with+triptolide+and+rapamycin+prolongs+graft+survival+in+a+mouse+model+of+cardiac+transplantationen_HK
dc.identifier.emailChen, Y:ychenc@hkucc.hku.hken_HK
dc.identifier.emailTam, PKH:paultam@hkucc.hku.hken_HK
dc.identifier.authorityChen, Y=rp01318en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1432-2277.2007.00630.xen_HK
dc.identifier.pmid18266776-
dc.identifier.scopuseid_2-s2.0-41749112206en_HK
dc.identifier.hkuros142085en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-41749112206&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume21en_HK
dc.identifier.issue5en_HK
dc.identifier.spage483en_HK
dc.identifier.epage494en_HK
dc.identifier.isiWOS:000255645300010-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLiu, Y=25928027200en_HK
dc.identifier.scopusauthoridChen, Y=36463185300en_HK
dc.identifier.scopusauthoridLiu, FQ=23993969500en_HK
dc.identifier.scopusauthoridLamb, JR=7201524642en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK

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