Abstract | BACKGROUND: AIM: The aim of this study was to test how global deletion of CD39 in mice impacts other models of experimental colitis. METHODS:
Colitis was induced in CD39-null and -wt mice, using trinitrobenzene sulfonic acid (TNBS, 125 mg/kg) administered intrarectally. Oxazolone colitis (1.5% oxazolone in 50% alcohol) was induced in comparable groups. Morphology, clinical and molecular parameters, and FACS analyses of lamina propria mononuclear cells (LPMC) were examined in CD39-null mice. CD39 expression was analyzed in human IBD biopsies. RESULTS: Paradoxically, TNBS colitis in CD39-null mice was characterized by improved survival, favorable clinical scores, and decreased MPO activity, when compared to wt mice (P < 0.05). LPMC from TNBS colitis contained significantly increased amounts of T-cells (CD3(+) and CD4(+)) and TNF-α mRNA expression were increased over those in CD39 null mice (P < 0.05). In contrast, oxazolone treated CD39-null and wt mice had comparable outcomes. In both ulcerative colitis and Crohn's disease, CD39 is present at high levels in intestinal tissue biopsies. CONCLUSIONS: TNBS colitis was attenuated in CD39-null mice whereas oxazolone-induced colitis was not impacted. Impaired adaptive cellular immune reactivity in the CD39-null environment appears protective in hapten-mediated Th1-type colitis. CD39 is expressed at high levels in clinical IBD tissues.
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Authors | Beat M Künzli, Pascal O Berberat, Karen Dwyer, Silvia Deaglio, Eva Csizmadia, Peter Cowan, Anthony d'Apice, Gregory Moore, Keiichi Enjyoji, Helmut Friess, Simon C Robson |
Journal | Digestive diseases and sciences
(Dig Dis Sci)
Vol. 56
Issue 5
Pg. 1393-403
(May 2011)
ISSN: 1573-2568 [Electronic] United States |
PMID | 20936356
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, CD
- Cytokines
- Oxazolone
- Trinitrobenzenesulfonic Acid
- Apyrase
- CD39 antigen
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Topics |
- Animals
- Antigens, CD
(genetics, metabolism)
- Apyrase
(genetics, metabolism)
- Colitis
(chemically induced, metabolism)
- Colon
(cytology, drug effects, metabolism, pathology)
- Cytokines
(genetics, metabolism)
- Humans
- Leukocytes, Mononuclear
(cytology)
- Mice
- Mice, Knockout
- Oxazolone
(toxicity)
- Specific Pathogen-Free Organisms
- Trinitrobenzenesulfonic Acid
(toxicity)
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