CD73 Is Critical for the Resolution of Murine Colonic Inflammation
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...
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| Format: | Article |
| Language: | en_US |
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Hindawi Publishing Corporation
2013
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| Online Access: | http://hdl.handle.net/1721.1/76703 |
| _version_ | 1826209199659417600 |
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| author | Bynoe, Margaret S. Waickman, Adam T. Mahamed, Deeqa A. Mueller, Cynthia Mills, Jeffrey H. Czopik, Agnieszka |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Bynoe, Margaret S. Waickman, Adam T. Mahamed, Deeqa A. Mueller, Cynthia Mills, Jeffrey H. Czopik, Agnieszka |
| author_sort | Bynoe, Margaret S. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:19:04Z |
| format | Article |
| id | mit-1721.1/76703 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:19:04Z |
| publishDate | 2013 |
| publisher | Hindawi Publishing Corporation |
| record_format | dspace |
| spelling | mit-1721.1/767032022-09-29T08:38:41Z CD73 Is Critical for the Resolution of Murine Colonic Inflammation Bynoe, Margaret S. Waickman, Adam T. Mahamed, Deeqa A. Mueller, Cynthia Mills, Jeffrey H. Czopik, Agnieszka Massachusetts Institute of Technology. Department of Biology Czopik, Agnieszka 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. National Institutes of Health (U.S.) (grant A1072434-A2) National Institutes of Health (U.S.) (grant R01NS063011) 2013-01-31T17:40:55Z 2013-01-31T17:40:55Z 2012-07 2012-07 Article http://purl.org/eprint/type/JournalArticle 1110-7243 1110-7251 http://hdl.handle.net/1721.1/76703 Bynoe, Margaret S. et al. “CD73 Is Critical for the Resolution of Murine Colonic Inflammation.” Journal of Biomedicine and Biotechnology 2012 (2012): 1–13. Web. en_US http://dx.doi.org/10.1155/2012/260983 Journal of Biomedicine and Biotechnology Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 application/pdf Hindawi Publishing Corporation Hindawi |
| spellingShingle | Bynoe, Margaret S. Waickman, Adam T. Mahamed, Deeqa A. Mueller, Cynthia Mills, Jeffrey H. Czopik, Agnieszka CD73 Is Critical for the Resolution of Murine Colonic Inflammation |
| title | CD73 Is Critical for the Resolution of Murine Colonic Inflammation |
| title_full | CD73 Is Critical for the Resolution of Murine Colonic Inflammation |
| title_fullStr | CD73 Is Critical for the Resolution of Murine Colonic Inflammation |
| title_full_unstemmed | CD73 Is Critical for the Resolution of Murine Colonic Inflammation |
| title_short | CD73 Is Critical for the Resolution of Murine Colonic Inflammation |
| title_sort | cd73 is critical for the resolution of murine colonic inflammation |
| url | http://hdl.handle.net/1721.1/76703 |
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