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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Expression of ecto-nucleoside triphosphate diphosphohydrolases-2 and -3 in the enteric nervous system affects inflammation in experimental colitis and Crohn's disease
Journal of Crohn's and Colitis, Volume 11, No. 9, Year 2017
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Description
Objective: Recent studies have suggested that the enteric nervous system can modulate gut immunity. Ecto-nucleoside triphosphate diphosphohydrolases [E-NTPDases] regulate purinergic signalling by sequential phosphohydrolysis of pro-inflammatory extracellular adenosine 5'-triphosphate [ATP]. Herein, we test the hypothesis that E-NTPDases modulate gut inflammation via neuro-immune crosstalk. Design: We determined expression patterns of NTPDase2 and NTPDase3 in murine and human colon. Experimental colitis was induced by dextran sodium sulphate [DSS] in genetically engineered mice deficient in NTPDase2 or NTPDase3. We compared plasma adenosine diphosphatase [ADPase] activity from Crohn's patients and healthy controls, and linked the enzyme activity to Crohn's disease activity. Results: NTPDase2 and -3 were chiefly expressed in cells of the enteric nervous system in both murine and human colon. When compared with wild type, DSS-induced colitis was exacerbated in Entpd2, and to a lesser extent, Entpd3 null mice as measured by disease activity score and histology, and marked anaemia was seen in both. Colonic macrophages isolated from Entpd2 null mice displayed a pro-inflammatory phenotype compared with wild type. In human plasma, Crohn's patients had decreases in ADPase activity when compared with healthy controls. The drop in ADPase activity was likely associated with changes in NTPDase2 and -3, as suggested by inhibitor studies, and were correlated with Crohn's disease activity. Conclusions: NTPDase2 and -3 are ecto-enzymes expressed in the enteric nervous system. Both enzymes confer protection against gut inflammation in experimental colitis and exhibit alterations in Crohn's disease. These observations suggest that purinergic signalling modulated by E-NTPDases governs neuro-immune interactions that are relevant in Crohn's disease. © 2017 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved.
Authors & Co-Authors
Csizmadia, Eva
United States, Boston
Beth Israel Deaconess Medical Center
Müller, Christa Elisabeth
Germany, Bonn
Universität Bonn
Robson, Simon Christopher
United States, Boston
Beth Israel Deaconess Medical Center
Statistics
Citations: 17
Authors: 3
Affiliations: 7
Identifiers
Doi:
10.1093/ecco-jcc/jjx058
ISSN:
18739946