Mechanism of action of IFN-beta in the treatment of multiple sclerosis: a special reference to CD73 and adenosine.
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.
Airas
Laura
L
Department of Neurology, University of Turku, PL52 20521 Turku, Finland. laura.airas@utu.fi
Niemelä
Jussi
J
Yegutkin
Gennady
G
Jalkanen
Sirpa
S
D015720:5'-Nucleotidase / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D016898:Interferon-alpha; D016899:Interferon-beta; D015720:5'-Nucleotidase; D000241:Adenosine