期刊
MOLECULAR IMMUNOLOGY
卷 45, 期 4, 页码 1191-1196出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2007.07.003
关键词
nitric oxide; experimental autoimmune encephalomyelitis; IL-12(-/-); IFN-gamma R-/-; NOS2(-/-)
The importance of the IL-12/IFN-gamma/nitric oxide (NO) axis in the pathogenesis of autoimmune diseases remains controversial. In parallel experiments, we explored the role of the IL-12/IFN-gamma/NO axis in the development of MOG 35-55-induced experimental autoimmune encephalomyelitis (EAE) in mice lacking IL-12, IFN-gamma receptor (IFN-gamma R) and inducible nitric oxide synthase (NOS2), respectively. In comparison with wide-type control mice, IL-12(-/-), IFN-gamma R-/- and NOS2(-/-) mice displayed more severe clinical signs of EAE both in remission and at subsequent relapse. Given the relatively low IFN-gamma production in IL-12(-/-) mice and the lack of IFN-gamma/IFN-gamma R signaling pathway in IFN-gamma R-/- mice, IL-12(-/-), IFN-gamma R-/- 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-gamma R-/- and NOS2(-/-) compared to control mice. In vitro experiments demonstrate that spleen mononuclear cells from IL-12(-/-), IFN-gamma R-/- and NOS2(-/-) mice with EAE present stronger migration capacity when compared to control mice. These results reveal that the IL-12/IFN-gamma/NO axis plays a critical role in the development of MOG 35-55-induced EAE, possibly over failing NO production. (c) 2007 Elsevier Ltd. All rights reserved.
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