Article: PPAR-γ signaling and IL-5 inhibition together prevent chronic rejection of MHC Class IImismatched cardiac grafts
| Title | PPAR-γ signaling and IL-5 inhibition together prevent chronic rejection of MHC Class IImismatched cardiac grafts | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Chen, Y1 2 Li, D1 Tsang, JYS1 Niu, N1 Peng, J1 Zhu, J1 Hui, K1 Xu, A1 Lui, VCH1 Lamb, JR3 Tam, PKH1 | ||||||
| Keywords | CD8 fibrosis IL-5 PPAR-γ vasculopathy | ||||||
| Issue Date | 2011 | ||||||
| Publisher | Elsevier 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?] DOI: http://dx.doi.org/10.1016/j.healun.2011.01.704 | ||||||
| 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. | ||||||
| ISSN | 1053-2498 2011 Impact Factor: 4.332 2011 SCImago Journal Rankings: 0.391 | ||||||
| DOI | http://dx.doi.org/10.1016/j.healun.2011.01.704 | ||||||
| ISI Accession Number ID | WOS:000290834600014
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 | References in Scopus | ||||||
| Grants | The role of adiponectin in cardiac allograft survival and immune regulation Analysis the modulation of M2 macrophages activation in response to TGF-\xE1 blockade |
| dc.contributor.author | Chen, Y | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Li, D | ||||||
| dc.contributor.author | Tsang, JYS | ||||||
| dc.contributor.author | Niu, N | ||||||
| dc.contributor.author | Peng, J | ||||||
| dc.contributor.author | Zhu, J | ||||||
| dc.contributor.author | Hui, K | ||||||
| dc.contributor.author | Xu, A | ||||||
| dc.contributor.author | Lui, VCH | ||||||
| dc.contributor.author | Lamb, JR | ||||||
| dc.contributor.author | Tam, PKH | ||||||
| dc.date.accessioned | 2011-07-27T01:36:36Z | ||||||
| dc.date.available | 2011-07-27T01:36:36Z | ||||||
| dc.date.issued | 2011 | ||||||
| dc.description.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. | ||||||
| dc.description.grant | The role of adiponectin in cardiac allograft survival and immune regulation | ||||||
| dc.description.grant | Analysis the modulation of M2 macrophages activation in response to TGF-\xE1 blockade | ||||||
| dc.description.grantcode | 98607 | ||||||
| dc.description.grantcode | 99865 | ||||||
| dc.description.nature | link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Journal 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.citeulike | 9076586 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1016/j.healun.2011.01.704 | ||||||
| dc.identifier.epage | 706 | ||||||
| dc.identifier.hkuros | 187596 | ||||||
| dc.identifier.isi | WOS:000290834600014
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.issn | 1053-2498 2011 Impact Factor: 4.332 2011 SCImago Journal Rankings: 0.391 | ||||||
| dc.identifier.issue | 6 | ||||||
| dc.identifier.pmid | 21435906 | ||||||
| dc.identifier.scopus | eid_2-s2.0-79955824245 | ||||||
| dc.identifier.spage | 698 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/135533 | ||||||
| dc.identifier.volume | 30 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/healun | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Journal of Heart and Lung Transplantation | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | Graft Rejection - immunology - prevention and control | ||||||
| dc.subject.mesh | Heart Transplantation - immunology | ||||||
| dc.subject.mesh | Immunosuppressive Agents - pharmacology - therapeutic use | ||||||
| dc.subject.mesh | Interleukin-5 - antagonists and inhibitors | ||||||
| dc.subject.mesh | Thiazolidinediones - pharmacology - therapeutic use | ||||||
| dc.subject | CD8 | ||||||
| dc.subject | fibrosis | ||||||
| dc.subject | IL-5 | ||||||
| dc.subject | PPAR-γ | ||||||
| dc.subject | vasculopathy | ||||||
| dc.title | PPAR-γ signaling and IL-5 inhibition together prevent chronic rejection of MHC Class IImismatched cardiac grafts | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine
- The University of Hong Kong
- Imperial College London