Počet záznamů: 1
MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function
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SYSNO ASEP 0472035 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function Tvůrce(i) 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) RIDCelkový počet autorů 17 Zdroj.dok. Mucosal Immunology. - : Springer - ISSN 1933-0219
Roč. 9, č. 4 (2016), s. 974-985Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova human matrix-metalloproteinase ; inflammatory-bowel-disease ; differential expression ; chemokine fractalkine ; epithelial-cells ; myeloid cells ; in-vivo ; mice ; tissue ; identification Vědní obor RIV EB - Genetika a molekulární biologie CEP GAP302/11/2048 GA ČR - Grantová agentura ČR GAP303/10/2044 GA ČR - Grantová agentura ČR ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UMG-J - RVO:68378050 UT WOS 000378346800013 DOI 10.1038/mi.2015.117 Anotace 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. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2017
Počet záznamů: 1