Mechanism of action of IFN-β in the treatment of multiple sclerosis -: A special reference to CD73 and adenosine

被引:27
作者
Airas, Laupa [1 ]
Niemela, Jussi [1 ]
Yegutkin, Gennady [1 ]
Jalkanen, Sirpa [1 ]
机构
[1] Turku Univ, Dept Neurol, Turku 20521, Finland
来源
AUTOIMMUNITY, PT B: NOVEL APPLICATIONS OF BASIC RESEARCH | 2007年 / 1110卷
关键词
multiple sclerosis; CD73; adenosine; IFN-beta;
D O I
10.1196/annals.1423.067
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IFN-beta treatment reduces the relapse rate in multiple sclerosis (MS), but the exact mechanism of action of the drug has remained elusive. CD73 (ecto-5'-nucleotidase) is an ectoenzyme, which produces adenosine from adenosine monophosphate (AMP) precursor by enzymatic dephosphorylation. AMP is known to be abundantly present at sites of inflammation, and more importantly adenosine, the product of CD73, is known to possess both anti-inflammatory and neuroprotective activity. Our preliminary work has shown that IFN-beta increases the expression of ecto-5'-nucleotidase on endothelial cells (ECs) both in vitro and after systemic treatment of MS patients in vivo. In the majority of MS patients also an increase in the soluble serum CD73 was noted after IFN-beta treatment. Importantly, this correlated with the clinical outcome. CD73 expression on central nervous system (CNS) microvasculature was confirmed with stainings of frozen tissue sections of MS brain samples taken at autopsy. Adenosine, a known neuroprotective agent, might contribute to the beneficial effects of IFN-beta on MS.
引用
收藏
页码:641 / 648
页数:8
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