A1 Journal article – refereed
IFN-alpha induced adenosine production on the endothelium: A mechanism mediated by CD73 (ecto-5 '-nucleotidase) up-regulation

List of Authors: Niemela J, Henttinen T, Yegutkin GG, Airas L, Kujari AM, Rajala P, Jalkanen S
Publication year: 2004
Journal: Journal of Immunology
Journal name in source: JOURNAL OF IMMUNOLOGY
Journal acronym: J IMMUNOL
Volume number: 172
Issue number: 3
ISSN: 0022-1767

CD73 (ecto-5'-nucleotidase; EC participates in lymphocyte binding to endothelial cells and converts extracellular AMP into a potent anti-inflammatory substance adenosine. However, the regulation of expression and function of CD73 has remained largely unknown. In this study, we show that IFN-alpha produces a time- and dose-dependent long-term up-regulation of CD73 on endothelial cells, but not on lymphocytes both at protein and RNA levels. Moreover, CD73-mediated production of adenosine is increased after IFN-alpha treatment on endothelial cells, resulting in a decrease in the permeability of these cells. Subsequent to induction with PMA, FMLP, dibutyryl cAMP, thrombin, histamine, IL-1beta, TNF-alpha, and LPS, no marked changes in the level of CD73 expression on endothelial cells are observed. We also show that CD73 is up-regulated in vivo on the vasculature after intravesical treatment of urinary bladder cancers with IFN-alpha. In conclusion, distinct behavior of lymphocyte and endothelial CD73 subsequent to cytokine treatment further emphasizes the existence of cell type-specific mechanisms in the regulation of CD73 expression and function. Overall, these results suggest that IFN-alpha is a relevant in vivo regulator of CD73 in the endothelial-leukocyte microenvironment in infections/inflammations, and thus has a fundamental role in controlling the extent of inflammation via CD73-dependent adenosine production.

Internal Authors/Editors

Last updated on 2019-19-07 at 16:58