| Extracorporeal photochemotherapy induces arginase 1 in patients with graft versus host disease. | |
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MedLine Citation:
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PMID: 21040785 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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The benefits of extracorporeal photochemotherapy (ECP; psoralen and UVA exposure of blood mononuclear cells) in graft-versus-host-disease (GVHD) are well-recognized, but the mechanisms of action remain elusive. As the metabolism of l-arginine in immune cells is known to play a role in immune tolerance, we investigated the effect of ECP on arginine metabolism, and the influence of extracellular l-arginine concentration on the response to ECP in cells from patients on therapy by ECP for a GVHD and healthy donors cultured before and after ECP in the presence of different concentrations of arginine (0, 50, 100, 200 and 1000 μmol/l). At baseline arginine was not metabolized through the same pathway in patients and donors. When cells were exposed to ECP, the production of ornithine but not NO° was enhanced, while mRNA of arginase 1 was up-regulated but not INOS. In GVHD patients, increasing arginine concentration resulted in down-regulation of IFNγ and TNFα mRNA expression, whereas IL10 was up-regulated especially at physiological plasma levels (between 0 and 100 μM). Overall, our study shows that ECP orients the metabolism of arginine toward the arginase pathway together with shifting the cytokine profile toward IL-10, providing new insights into the enigmatic mechanism of action of ECP. |
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Authors:
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E Merlin; N Goncalves-Mendes; D Hannani; A de la Torre; M C Farges; H Laroye; F Demeocq; J Kanold; M P Vasson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-30 |
Journal Detail:
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Title: Transplant immunology Volume: 24 ISSN: 1878-5492 ISO Abbreviation: Transpl. Immunol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9309923 Medline TA: Transpl Immunol Country: England |
Other Details:
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Languages: eng Pagination: 100-6 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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CHU Clermont-Ferrand, Centre Régional de Cancérologie et Thérapie Cellulaire Pédiatrique, Hôtel-Dieu, France. e_merlin@chu-clermontferrand.fr |
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