کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2832995 | 1163853 | 2008 | 6 صفحه PDF | دانلود رایگان |

The importance of the IL-12/IFN-γ/nitric oxide (NO) axis in the pathogenesis of autoimmune diseases remains controversial. In parallel experiments, we explored the role of the IL-12/IFN-γ/NO axis in the development of MOG 35-55-induced experimental autoimmune encephalomyelitis (EAE) in mice lacking IL-12, IFN-γ receptor (IFN-γR) and inducible nitric oxide synthase (NOS2), respectively. In comparison with wide-type control mice, IL-12−/−, IFN-γR−/− and NOS2−/− mice displayed more severe clinical signs of EAE both in remission and at subsequent relapse. Given the relatively low IFN-γ production in IL-12−/− mice and the lack of IFN-γ/IFN-γR signaling pathway in IFN-γR−/− mice, IL-12−/−, IFN-γR−/− and NOS2−/− mice with EAE exhibited low NO production. This correlated negatively with MOG 35-55-induced T cell proliferation. Both ED1-positive macrophages and CD4-positive T cells were increased in spinal cords from IL-12−/−, IFN-γR−/− and NOS2−/− compared to control mice. In vitro experiments demonstrate that spleen mononuclear cells from IL-12−/−, IFN-γR−/− and NOS2−/− mice with EAE present stronger migration capacity when compared to control mice. These results reveal that the IL-12/IFN-γ/NO axis plays a critical role in the development of MOG 35-55-induced EAE, possibly over failing NO production.
Journal: Molecular Immunology - Volume 45, Issue 4, February 2008, Pages 1191–1196