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Citation

BibTex format

@article{Barry:2020:10.1038/s41385-019-0235-4,
author = {Barry, R and Ruano-Gallego, D and Radhakrishnan, ST and Lovell, S and Yu, L and Kotik, O and Glegola-Madejska, I and Tate, EW and Choudhary, JS and Williams, HRT and Frankel, G},
doi = {10.1038/s41385-019-0235-4},
journal = {Mucosal Immunology},
pages = {322--333},
title = {Faecal neutrophil elastase-antiprotease balance reflects colitis severity},
url = {http://dx.doi.org/10.1038/s41385-019-0235-4},
volume = {13},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Given the global burden of diarrheal diseases on healthcare it is surprising how little is known about the drivers of disease severity. Colitis caused by infection and inflammatory bowel disease (IBD) is characterised by neutrophil infiltration into the intestinal mucosa and yet our understanding of neutrophil responses during colitis is incomplete. Using infectious (Citrobacter rodentium) and chemical (dextran sulphate sodium; DSS) murine colitis models, as well as human IBD samples, we find that faecal neutrophil elastase (NE) activity reflects disease severity. During C. rodentium infection intestinal epithelial cells secrete the serine protease inhibitor SerpinA3N to inhibit and mitigate tissue damage caused by extracellular NE. Mice suffering from severe infection produce insufficient SerpinA3N to control excessive NE activity. This activity contributes to colitis severity as infection of these mice with a recombinant C. rodentium strain producing and secreting SerpinA3N reduces tissue damage. Thus, uncontrolled luminal NE activity is involved in severe colitis. Taken together, our findings suggest that NE activity could be a useful faecal biomarker for assessing disease severity as well as therapeutic target for both infectious and chronic inflammatory colitis.
AU  - Barry,R
AU  - Ruano-Gallego,D
AU  - Radhakrishnan,ST
AU  - Lovell,S
AU  - Yu,L
AU  - Kotik,O
AU  - Glegola-Madejska,I
AU  - Tate,EW
AU  - Choudhary,JS
AU  - Williams,HRT
AU  - Frankel,G
DO  - 10.1038/s41385-019-0235-4
EP  - 333
PY  - 2020///
SN  - 1933-0219
SP  - 322
TI  - Faecal neutrophil elastase-antiprotease balance reflects colitis severity
T2  - Mucosal Immunology
UR  - http://dx.doi.org/10.1038/s41385-019-0235-4
UR  - https://www.nature.com/articles/s41385-019-0235-4
UR  - http://hdl.handle.net/10044/1/75226
VL  - 13
ER  -
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Prof. Ed Tate
GSK Chair in Chemical Biology
Department of Chemistry
Molecular Sciences Research Hub, White City Campus,
82 Wood Lane, London, W12 0BZ

e.tate@imperial.ac.uk
Tel: +44 (0)20 759 + ext 43752 or 45821