期刊
METABOLIC BRAIN DISEASE
卷 26, 期 2, 页码 107-113出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11011-011-9239-9
关键词
hAAT; EAE; Tregs; Pro-inflammatory cytokines; CCR6
资金
- Biomedical Laboratory R&D Service, Department of Veterans' Affairs
- Israel Science Foundation [1027/07]
Alpha-1-antitrypsin (AAT) is the primary circulating serine protease inhibitor, and is known to exert potent anti-inflammatory effects and to inhibit the progression of several autoimmune diseases. In this study, transgenic mice that over-express surfactant-driven human (h)AAT on the C57BL/6 background were evaluated for resistance to MOG-35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE), compared to WT C57BL/6 control mice. According to the results, sustained levels of circulating hAAT profoundly inhibited induction of clinical signs, inflammatory lesions and demyelination observed in WT mice with EAE, concomitant with enhanced levels of CD4+FoxP3+ Treg cells, reduced secretion of MOG peptide-induced pro-inflammatory cytokines, IL-17, IL-1 beta & IL-6, diminished expression of caspase-1 and enhanced expression of CCR6. These results implicate hAAT as a potent immunoregulatory agent worthy of further investigation as a potential therapy in human autoimmune diseases including multiple sclerosis.
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