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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 260983, 13 pages
http://dx.doi.org/10.1155/2012/260983
Research Article

CD73 Is Critical for the Resolution of Murine Colonic Inflammation

1Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, C5 149 VMC, Ithaca, NY 14853, USA
2Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

Received 14 May 2012; Revised 7 July 2012; Accepted 11 July 2012

Academic Editor: Linda F. Thompson

Copyright © 2012 Margaret S. Bynoe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

CD73 is a glycosyl-phosphatidylinositol-(GPI-) linked membrane protein that catalyzes the extracellular dephosphorylation of adenosine monophosphate (AMP) to adenosine. Adenosine is a negative regulator of inflammation and prevents excessive cellular damage. We investigated the role of extracellular adenosine in the intestinal mucosa during the development of Dextran-Sulfate-Sodium-(DSS-)salt-induced colitis in mice that lack CD73 (CD73−/−) and are unable to synthesize extracellular adenosine. We have found that, compared to wild-type (WT) mice, CD73−/− mice are highly susceptible to DSS-induced colitis. CD73−/− mice exhibit pronounced weight loss, slower weight recovery, an increase in gut permeability, a decrease in expression of tight junctional adhesion molecules, as well as unresolved inflammation following the removal of DSS. Moreover, colonic epithelia in CD73−/− mice exhibited increased TLR9 expression, high levels of IL-1β and TNF-α, and constitutive activation of NF-κB. We conclude that CD73 expression in the colon is critical for regulating the magnitude and the resolution of colonic immune responses.