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Article: PPAR-γ signaling and IL-5 inhibition together prevent chronic rejection of MHC Class IImismatched cardiac grafts
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TitlePPAR-γ signaling and IL-5 inhibition together prevent chronic rejection of MHC Class IImismatched cardiac grafts
 
AuthorsChen, Y1 2
Li, D1
Tsang, JYS1
Niu, N1
Peng, J1
Zhu, J1
Hui, K1
Xu, A1
Lui, VCH1
Lamb, JR3
Tam, PKH1
 
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
 
CitationJournal Of Heart And Lung Transplantation, 2011, v. 30 n. 6, p. 698-706 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.healun.2011.01.704
 
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.
 
ISSN1053-2498
2013 Impact Factor: 5.611
2013 SCImago Journal Rankings: 2.881
 
DOIhttp://dx.doi.org/10.1016/j.healun.2011.01.704
 
ISI Accession Number IDWOS:000290834600014
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).

 
ReferencesReferences in Scopus
 
GrantsThe role of adiponectin in cardiac allograft survival and immune regulation
 
DC FieldValue
dc.contributor.authorChen, Y
 
dc.contributor.authorLi, D
 
dc.contributor.authorTsang, JYS
 
dc.contributor.authorNiu, N
 
dc.contributor.authorPeng, J
 
dc.contributor.authorZhu, J
 
dc.contributor.authorHui, K
 
dc.contributor.authorXu, A
 
dc.contributor.authorLui, VCH
 
dc.contributor.authorLamb, JR
 
dc.contributor.authorTam, PKH
 
dc.date.accessioned2011-07-27T01:36:36Z
 
dc.date.available2011-07-27T01:36:36Z
 
dc.date.issued2011
 
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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Heart And Lung Transplantation, 2011, v. 30 n. 6, p. 698-706 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.healun.2011.01.704
 
dc.identifier.citeulike9076586
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.healun.2011.01.704
 
dc.identifier.epage706
 
dc.identifier.hkuros187596
 
dc.identifier.isiWOS:000290834600014
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).

 
dc.identifier.issn1053-2498
2013 Impact Factor: 5.611
2013 SCImago Journal Rankings: 2.881
 
dc.identifier.issue6
 
dc.identifier.pmid21435906
 
dc.identifier.scopuseid_2-s2.0-79955824245
 
dc.identifier.spage698
 
dc.identifier.urihttp://hdl.handle.net/10722/135533
 
dc.identifier.volume30
 
dc.languageeng
 
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/healun
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Heart and Lung Transplantation
 
dc.relation.projectThe role of adiponectin in cardiac allograft survival and immune regulation
 
dc.relation.referencesReferences in Scopus
 
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.subjectCD8
 
dc.subjectfibrosis
 
dc.subjectIL-5
 
dc.subjectPPAR-γ
 
dc.subjectvasculopathy
 
dc.titlePPAR-γ signaling and IL-5 inhibition together prevent chronic rejection of MHC Class IImismatched cardiac grafts
 
dc.typeArticle
 
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<contributor.author>Niu, N</contributor.author>
<contributor.author>Peng, J</contributor.author>
<contributor.author>Zhu, J</contributor.author>
<contributor.author>Hui, K</contributor.author>
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<description.abstract>Background: Chronic rejection can prevent long-term survival of organ transplants. Although the beneficial effects of peroxisome proliferator- activated receptor-gamma (PPAR-&#947;) 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-&#947; 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-&#947; signaling combined with IL-5 blockade prevents graft rejection. &#169; 2011 International Society for Heart and Lung Transplantation. All rights reserved.</description.abstract>
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. The University of Hong Kong
  3. Imperial College London