| Literature DB >> 17684157 |
Dominique Chabannes1, Marcelo Hill, Emmanuel Merieau, Julien Rossignol, Régis Brion, Jean Paul Soulillou, Ignacio Anegon, Maria Cristina Cuturi.
Abstract
Mesenchymal stem cells (MSCs) display immunomodulatory properties mediated by various factors, including inducible nitric oxide synthase (iNOS). Since heme oxygenase-1 (HO-1) is a potent immunosuppressive enzyme, we tested the hypothesis that HO-1 could mediate the immunosuppressive effects of MSCs. We generated adult rat MSCs that inhibited T-cell proliferation in vitro. These MSCs expressed both HO-1 and iNOS. In vitro, whereas neither HO-1 nor iNOS inhibition alone could interfere with the immunosuppressive properties of rat MSCs, simultaneous inhibition of both enzymes restored T-cell proliferation. In vivo, injection of MSCs significantly delayed heart allograft rejection, and inhibition of either HO-1 or iNOS totally reversed the protective activity of MSCs, inducing rejection. Adult human MSCs also expressed HO-1; in these cells, HO-1 inhibition was sufficient to completely block their immunosuppressive capacity. In conclusion, we show, for the first time, that HO-1 mediates the immunosuppressive properties of rat and human MSCs.Entities:
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Year: 2007 PMID： 17684157 DOI： 10.1182/blood-2007-02-075481
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113