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

Brauer, Rena; Turečková, Jolana; Kanchev, Ivan; Khoylou, M.; Škarda, J.; Procházka, Jan; Špoutil, František; Beck, Inken; Žbodáková, Olga; Kašpárek, Petr; Kořínek, Vladimír; Chalupský, Karel; Karhu, T.; Herzig, K.H.; Hajduch, M.; Gregor, Martin; Sedláček, Radislav

doi:https://dx.doi.org/10.1038/mi.2015.117

Number of the records: 1

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

1.

SYSNO ASEP	0472035
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function
Author(s)	Brauer, Rena (UMG-J) Turečková, Jolana (UMG-J)_RID Kanchev, Ivan (UMG-J)_RID Khoylou, M. (CZ) Škarda, J. (CZ) Procházka, Jan (UMG-J)_ORCID Špoutil, František (UMG-J) Beck, Inken (UMG-J)_RID Žbodáková, Olga (UMG-J) Kašpárek, Petr (UMG-J) Kořínek, Vladimír (UMG-J)_RID Chalupský, Karel (UMG-J) Karhu, T. (FI) Herzig, K.H. (FI) Hajduch, M. (CZ) Gregor, Martin (UMG-J)_{RID, ORCID} Sedláček, Radislav (UMG-J)_RID
Number of authors	17
Source Title	Mucosal Immunology. - : Springer - ISSN 1933-0219 Roč. 9, č. 4 (2016), s. 974-985
Number of pages	12 s.
Language	eng - English
Country	US - United States
Keywords	human matrix-metalloproteinase ; inflammatory-bowel-disease ; differential expression ; chemokine fractalkine ; epithelial-cells ; myeloid cells ; in-vivo ; mice ; tissue ; identification
Subject RIV	EB - Genetics ; Molecular Biology
R&D Projects	GAP302/11/2048 GA ČR - Czech Science Foundation (CSF)
	GAP303/10/2044 GA ČR - Czech Science Foundation (CSF)
	ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Institutional support	UMG-J - RVO:68378050
UT WOS	000378346800013
DOI	10.1038/mi.2015.117
Annotation	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.
Workplace	Institute of Molecular Genetics
Contact	Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
Year of Publishing	2017

Number of the records: 1