MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F16%3A00472035" target="_blank" >RIV/68378050:_____/16:00472035 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/16:10337156 RIV/61989592:15110/16:33160828

Result on the web

<a href="http://dx.doi.org/10.1038/mi.2015.117" target="_blank" >http://dx.doi.org/10.1038/mi.2015.117</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/mi.2015.117" target="_blank" >10.1038/mi.2015.117</a>

Result language

angličtina

Original language name

MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function

Original language description

Matrix metalloproteinases (MMPs) are potential biomarkers for disease activity in inflammatory bowel disease (IBD). However, clinical trials targeting MMPs have not succeeded, likely due to poor understanding of the biological functions of individual MMPs. Here, we explore the role of MMP-19 in IBD pathology. Using a DSS-induced model of colitis, we show evidence for increased susceptibility of Mmp-19-deficient (Mmp-19(-/-)) mice to colitis. Absence of MMP-19 leads to significant disease progression, with reduced survival rates, severe tissue destruction, and elevated levels of proinflammatory modulators in the colon and plasma, and failure to resolve inflammation. There was a striking delay in neutrophil infiltration into the colon of Mmp-19(-/-) mice during the acute colitis, leading to persistent inflammation and poor recovery; this was rescued by reconstitution of irradiated Mmp-19(-/-)mice with wild-type bone marrow. Additionally, Mmp-19-deficient macrophages exhibited decreased migration in vivo and in vitro and the mucosal barrier appeared compromised. Finally, chemokine fractalkine (CX3CL1) was identified as a novel substrate of MMP-19, suggesting a link between insufficient processing of CX3CL1 and cell recruitment in the Mmp-19(-/-) mice. MMP-19 proves to be a critical factor in balanced host response to colonic pathogens, and for orchestrating appropriate innate immune response in colitis.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Mucosal Immunology

ISSN

1933-0219

e-ISSN

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Volume of the periodical

9

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

974-985

UT code for WoS article

000378346800013

EID of the result in the Scopus database

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