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Article: PPAR-γ signaling and IL-5 inhibition together prevent chronic rejection of MHC Class IImismatched cardiac grafts

TitlePPAR-γ signaling and IL-5 inhibition together prevent chronic rejection of MHC Class IImismatched cardiac grafts
Authors
KeywordsCD8
fibrosis
IL-5
PPAR-γ
vasculopathy
Issue Date2011
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/healun
Citation
Journal Of Heart And Lung Transplantation, 2011, v. 30 n. 6, p. 698-706 How to Cite?
Abstract
Background: Chronic rejection can prevent long-term survival of organ transplants. Although the beneficial effects of peroxisome proliferator- activated receptor-gamma (PPAR-γ) in reducing graft rejection have been reported, the details of the underlying mechanisms remain unclear, especially in the context of modulating cellular infiltration and preventing vasculopathy and interstitial fibrosis. Methods: The therapeutic effects of the PPAR-γ agonist, rosiglitazone, combined with antiinterleukin-5 are explored in a mouse model of MHC Class IIhistoincompatible cardiac transplantation. Results: Rosiglitazone treatment alone marginally increased long-term survival and reduced CD8 T-cell infiltration and vasculopathy in the grafts. However, there was no reduction in collagen deposition and interleukin (IL)-4, IL-5 and eosinophil infiltration were increased. AntiIL-5 antibody treatment alone reduced eosinophil infiltration and collagen deposition, but had no effect on CD8 T-cell infiltration or vasculopathy. Combined treatment with antiIL-5 antibody and rosiglitazone prevented graft rejection. Furthermore, rosiglitazone treatment increased adiponectin receptor II expression in grafts and on dendritic cells and T cells in vitro. Graft survival correlated with increased expression in grafts of the inhibitory molecule PD-L1. Conclusions: The findings obtained increase the knowledge on the mode of action of rosiglitazone in promoting the survival of MHC Class IImismatched cardiac transplants in which the CD8 T cells and eosinophils play key roles. PPAR-γ signaling combined with IL-5 blockade prevents graft rejection. © 2011 International Society for Heart and Lung Transplantation. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/135533
ISSN
2013 Impact Factor: 5.611
2013 SCImago Journal Rankings: 2.881
ISI Accession Number ID
Funding AgencyGrant Number
General Research FundHKU 762108M
University of Hong Kong200811159035
Funding Information:

The first two authors (Y.C. and D.-X.L.) contributed equally to this work. The project was supported by the General Research Fund (HKU 762108M) and the Seed Funding Programme for Basic Research, University of Hong Kong (200811159035).

References
Grants

 

Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. The University of Hong Kong
  3. Imperial College London
DC FieldValueLanguage
dc.contributor.authorChen, Yen_HK
dc.contributor.authorLi, Den_HK
dc.contributor.authorTsang, JYSen_HK
dc.contributor.authorNiu, Nen_HK
dc.contributor.authorPeng, Jen_HK
dc.contributor.authorZhu, Jen_HK
dc.contributor.authorHui, Ken_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorLui, VCHen_HK
dc.contributor.authorLamb, JRen_HK
dc.contributor.authorTam, PKHen_HK
dc.date.accessioned2011-07-27T01:36:36Z-
dc.date.available2011-07-27T01:36:36Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Heart And Lung Transplantation, 2011, v. 30 n. 6, p. 698-706en_HK
dc.identifier.issn1053-2498en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135533-
dc.description.abstractBackground: Chronic rejection can prevent long-term survival of organ transplants. Although the beneficial effects of peroxisome proliferator- activated receptor-gamma (PPAR-γ) in reducing graft rejection have been reported, the details of the underlying mechanisms remain unclear, especially in the context of modulating cellular infiltration and preventing vasculopathy and interstitial fibrosis. Methods: The therapeutic effects of the PPAR-γ agonist, rosiglitazone, combined with antiinterleukin-5 are explored in a mouse model of MHC Class IIhistoincompatible cardiac transplantation. Results: Rosiglitazone treatment alone marginally increased long-term survival and reduced CD8 T-cell infiltration and vasculopathy in the grafts. However, there was no reduction in collagen deposition and interleukin (IL)-4, IL-5 and eosinophil infiltration were increased. AntiIL-5 antibody treatment alone reduced eosinophil infiltration and collagen deposition, but had no effect on CD8 T-cell infiltration or vasculopathy. Combined treatment with antiIL-5 antibody and rosiglitazone prevented graft rejection. Furthermore, rosiglitazone treatment increased adiponectin receptor II expression in grafts and on dendritic cells and T cells in vitro. Graft survival correlated with increased expression in grafts of the inhibitory molecule PD-L1. Conclusions: The findings obtained increase the knowledge on the mode of action of rosiglitazone in promoting the survival of MHC Class IImismatched cardiac transplants in which the CD8 T cells and eosinophils play key roles. PPAR-γ signaling combined with IL-5 blockade prevents graft rejection. © 2011 International Society for Heart and Lung Transplantation. All rights reserved.en_HK
dc.languageengen_US
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/healunen_HK
dc.relation.ispartofJournal of Heart and Lung Transplantationen_HK
dc.subjectCD8en_HK
dc.subjectfibrosisen_HK
dc.subjectIL-5en_HK
dc.subjectPPAR-γen_HK
dc.subjectvasculopathyen_HK
dc.subject.meshGraft Rejection - immunology - prevention and control-
dc.subject.meshHeart Transplantation - immunology-
dc.subject.meshImmunosuppressive Agents - pharmacology - therapeutic use-
dc.subject.meshInterleukin-5 - antagonists and inhibitors-
dc.subject.meshThiazolidinediones - pharmacology - therapeutic use-
dc.titlePPAR-γ signaling and IL-5 inhibition together prevent chronic rejection of MHC Class IImismatched cardiac graftsen_HK
dc.typeArticleen_HK
dc.identifier.emailChen, Y: ychenc@hkucc.hku.hken_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.emailLui, VCH: vchlui@hkucc.hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hkucc.hku.hken_HK
dc.identifier.authorityChen, Y=rp01318en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.identifier.authorityLui, VCH=rp00363en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.healun.2011.01.704en_HK
dc.identifier.pmid21435906en_HK
dc.identifier.scopuseid_2-s2.0-79955824245en_HK
dc.identifier.hkuros187596en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955824245&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume30en_HK
dc.identifier.issue6en_HK
dc.identifier.spage698en_HK
dc.identifier.epage706en_HK
dc.identifier.isiWOS:000290834600014-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectThe role of adiponectin in cardiac allograft survival and immune regulation-
dc.identifier.scopusauthoridChen, Y=36463185300en_HK
dc.identifier.scopusauthoridLi, D=49961792800en_HK
dc.identifier.scopusauthoridTsang, JYS=15081781300en_HK
dc.identifier.scopusauthoridNiu, N=49962019600en_HK
dc.identifier.scopusauthoridPeng, J=49961959700en_HK
dc.identifier.scopusauthoridZhu, J=7405690800en_HK
dc.identifier.scopusauthoridHui, K=35764515100en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridLui, VCH=7004231344en_HK
dc.identifier.scopusauthoridLamb, JR=7201524642en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK
dc.identifier.citeulike9076586-

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