IFN-β regulates CD73 and adenosine expression at the blood-brain barrier

Jussi Niemelä, Igal Ifergan, Gennady G. Yegutkin, Sirpa Jalkanen, Alexander Prat, Laura Airas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

IFN-β treatment reduces the relapse rate in MS but its mechanism of action remains incompletely understood. Our aim was to clarify the beneficial effect of IFN-β in the treatment of MS. We assessed the influence of IFN-β treatment on (i) CD73 expression on the surface of primary cultures of human blood-brain barrier endothelial cells (BBB-EC) and human astrocytes using immunofluorescence staining and flow cytometry, (ii) transmigration of CD4 + T lymphocytes using an in vitro model of BBB and (iii) CD73 enzyme activity, i.e. ecto-5′-nucleotidase activity in the serum of MS patients using a radiochemical assay. IFN-β increases the expression of ecto-5′-nucleotidase both on BBB-EC and astrocytes. As a consequence, lymphocyte transmigration through BBB-EC is reduced. Importantly, this reduction can be reversed using α,β-methyleneadenosine-5′-diphosphate, a specific inhibitor of ecto-5′-nucleotidase. CD73 is strongly expressed in microvasculature in samples of postmortem MS brain and, moreover, in the majority of MS patients there was a clear upregulation both in the soluble serum ecto-5′-nucleotidase activity and skin microvascular CD73 expression after IFN-β treatment. Upregulation of ecto-5′-nucleotidase and a subsequent increase in adenosine production might contribute to the beneficial effects of IFN-β on MS via enhancing the endothelial barrier function.

Original languageEnglish (US)
Pages (from-to)2718-2726
Number of pages9
JournalEuropean Journal of Immunology
Volume38
Issue number10
DOIs
StatePublished - Dec 1 2008

Keywords

  • Adenosine
  • Blood-brain barrier
  • CD73
  • IFN-β
  • MS

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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