Gene transfer of soluble interleukin-17 receptor prolongs cardiac allograft survival in a rat model

Détails

Ressource 1Télécharger: REF.pdf (234.80 [Ko])
Etat: Public
Version: Final published version
Licence: Non spécifiée
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
ID Serval
serval:BIB_D90F2266E49F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Gene transfer of soluble interleukin-17 receptor prolongs cardiac allograft survival in a rat model
Périodique
European Journal of Cardio-Thoracic Surgery
Auteur⸱e⸱s
Li  J., Simeoni  E., Fleury  S., Dudler  J., Fiorini  E., Kappenberger  L., von Segesser  L. K., Vassalli  G.
ISSN
1010-7940 (Print)
Statut éditorial
Publié
Date de publication
05/2006
Volume
29
Numéro
5
Pages
779-83
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Résumé
OBJECTIVE: Interleukin-17 (IL-17), a potent proinflammatory cytokine, has been implicated in allograft rejection. We analyzed the efficacy of an adenoviral vector expressing an IL-17 inhibitor in delaying acute allograft rejection in a rat model of heart transplantation, and the biological mechanisms underlying the protective effect. METHODS: We constructed an adenoviral vector expressing a soluble IL-17 receptor-immunoglobulin (IL-17R-Ig) fusion protein. IL-17R-Ig activity was assessed by inhibition of IL-17-induced IL-6 release in HeLa cells preincubated with the vector. Intracoronary vector administration was performed in F344 donor hearts that were placed as vascularized grafts into Lewis hosts. Inflammatory cells infiltrating the graft were analyzed by immunohistology. Cytokine transcripts in the graft were determined by real-time RT-PCR. RESULTS: IL-17R-Ig gene transfer resulted in prolonged allograft survival (16.1+/-3.1 days vs 10.3+/-2.5 days with control virus and 10.1+/-2.1 days with virus dilution buffer alone; p<0.001). IL-17R-Ig gene transfer reduced inflammatory cell infiltrates, especially monocytes/macrophages and CD4+ T cells (p<0.05). It also reduced intragraft cytokine transcripts for interferon-gamma and transforming growth factor-beta (p<0.05) and, to a lesser extent, IL-1beta and tumor necrosis factor-alpha (p=0.083). CONCLUSIONS: Local expression of soluble IL-17 receptor-immunoglobulin attenuates T helper type 1 (Th1) cytokine responses and leukocyte infiltration in rat cardiac allografts, thereby mediating prolonged graft survival. Intragraft IL-17 inhibition may be useful as an adjuvant therapy to systemic immunosuppression in heart transplantation.
Mots-clé
Adenoviridae/genetics Animals CD4-Positive T-Lymphocytes/immunology Cytokines/biosynthesis/genetics Gene Therapy/*methods *Gene Transfer Techniques Genetic Vectors Graft Rejection/immunology/*prevention & control Graft Survival/immunology *Heart Transplantation Male Mice Mice, Inbred C57BL Monocytes/immunology Rats Rats, Inbred F344 Rats, Inbred Lew Receptors, Interleukin/genetics/*physiology Receptors, Interleukin-17 Reverse Transcriptase Polymerase Chain Reaction/methods Solubility
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/02/2008 11:29
Dernière modification de la notice
14/02/2022 7:57
Données d'usage