The heat shock response reduces myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in mice

被引:33
作者
Heneka, MT
Sharp, A
Murphy, P
Lyons, JA
Dumitrescu, L
Feinstein, DL
机构
[1] Univ Bonn, Dept Neurol, D-5300 Bonn, Germany
[2] Univ Illinois, Dept Anesthesiol, Chicago, IL USA
[3] Washington Univ, Sch Med, Dept Neurol, St Louis, MO USA
关键词
cytokines; demyelinating disease; heat shock; inflammation; nitric oxide;
D O I
10.1046/j.1471-4159.2001.00260.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The stress response (SR) can block inflammatory gene expression by preventing activation of transcription factor nuclear factor-kappa B (NF-KB). As inflammatory gene expression contributes to the pathogenesis of demyelinating diseases, we tested the effects of the SR on the progression of the demyelinating disease experimental autoimmune encephalomyelitis (EAE). EAE was actively induced in C57BL/6 mice using an encephalitogenic myelin oligodendrocyte glycoprotein (MOG(35-55)) peptide. Whole body hyperthermia was used to induce a heat shock response (HSR) in immunized mice 2 days after the booster MOG35-55 peptide injection. The HSR reduced the incidence of EAE by 70%, delayed disease onset by 6 days, and attenuated disease severity. The HSR attenuated leukocyte infiltration into CNS assessed by quantitation of perivascular infiltrates, and by reduced staining for CD4 and CD25 immunopositive T-cells. T-cell activation, assessed by the production of interferon gamma (IFN I) in response to MOG(35-55), was also decreased by the HSR. The HSR reduced inflammatory gene expression in the brain that normally occurs during EAE, including the early increase in RANTES (regulated on activation of normal T-cell expressed and secreted) expression, and the later expression of the inducible form of nitric oxide synthase. The early activation of transcription factor NF-KB was also blocked by the HSR. The finding that the SR reduces inflammation in the brain and the clinical severity of EAE opens a novel therapeutic approach for prevention of autoimmune diseases.
引用
收藏
页码:568 / 579
页数:12
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