Xu, Tao and Haering, Cristina and Lau, Chi-Keung and Obed, Aiman and Ma, Jian and Doenecke, Axel and Scherer, Marcus N. and Schnitzbauer, Andreas A. and Fan, Sheung-Tat and Schlitt, Hans J. and Tsui, Tung-Yu (2008) Targeting of interleukin-10 is superior to cytotoxic T-lymphocyte associated antigen 4 with human immunoglobulin G(1) for the prevention of chronic allograft deterioration in organ transplantation. JOURNAL OF GENE MEDICINE, 10 (12). pp. 1315-1323. ISSN 1099-498X,
Full text not available from this repository. (Request a copy)Abstract
Background Genetic manipulation of the allograft is an attractive approach to prevent the graft against chronic deterioration through stable expression of immunomodulatory or protective genes. However, the best strategy for prevention of chronic allograft deterioration remains unclear. Methods The efficacies of adeno-associated viral vector-mediated stable expression of indoleamine 2,3-dioxygenase (IDO), cytotoxic T-lymphocyte associated antigen 4 with human immunoglobulin G, (CTLA4Ig) or interleukin-10 (IL-10) in the prevention of chronic allograft deterioration were compared in a rat heart transplantation model. Results Transduction of grafts with IL-10 significantly prolonged allograft survival, whereas transduction of grafts with IDO did not improve graft survival compared to controls. Analysis of long-term survived heart allografts showed that both CTLA4Ig and IL-10 could significantly reduced the T cells and macrophage infiltration. However, stable expression of CTLA4Ig failed to prevent the development of transplant arteriosclerosis. By contrast, IL-10 suppressed the development of transplant arteriosclerosis effectively. The suppressive effects of IL-10 in preventing the development of chronic allograft deterioration were associated with lower transcript levels of transforming tumor growth factor beta 1 and macrophage migration inhibitory factor in the graft. In addition, higher transcript levels of heme oxygenase-1 were found in IL-10-transduced allograft. Conclusions Targeting on IL-10 is superior to CTLA4Ig or IDO for the treatment of chronic allograft deterioration. Copyright (C) 2008 John Wiley & Sons, Ltd.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENE-TRANSFER; HEME OXYGENASE-1; INDOLEAMINE 2,3-DIOXYGENASE; TRYPTOPHAN CATABOLISM; NITRIC-OXIDE; SURVIVAL; VIRUS; REJECTION; CTLA4IG; LIVER; adeno-associated viral vector; chronic rejection; gene therapy; interleukin-10; transplant arteriosclerosis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Oct 2020 10:42 |
| Last Modified: | 16 Oct 2020 10:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29978 |
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