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J Immunol. 2016 Jul 1;197(1):296-302. doi: 10.4049/jimmunol.1600094. Epub 2016 Jun 3.

MMP-25 Metalloprotease Regulates Innate Immune Response through NF-κB Signaling.

Author information

1
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain;
2
Institute for Cancer Genetics, Columbia University, New York, NY 10032;
3
Servivio de Hematología, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain;
4
Servicio de Anatomía Patológica, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain;
5
Laboratorio de Proteómica Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain; and.
6
Área de Fisiología, Departamento de Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain.
7
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain; clo@uniovi.es.

Abstract

Matrix metalloproteases (MMPs) regulate innate immunity acting over proinflammatory cytokines, chemokines, and other immune-related proteins. MMP-25 (membrane-type 6-MMP) is a membrane-bound enzyme predominantly expressed in leukocytes whose biological function has remained largely unknown. We have generated Mmp25-deficient mice to elucidate the in vivo function of this protease. These mutant mice are viable and fertile and do not show any spontaneous phenotype. However, Mmp25-null mice exhibit a defective innate immune response characterized by low sensitivity to bacterial LPS, hypergammaglobulinemia, and reduced secretion of proinflammatory molecules. Moreover, these immune defects can be tracked to a defective NF-κB activation observed in Mmp25-deficient leukocytes. Globally, our findings provide new mechanistic insights into innate immunity through the activity of MMP-25, suggesting that this proteinase could be a potential therapeutic target for immune-related diseases.

PMID:
27259858
DOI:
10.4049/jimmunol.1600094
[Indexed for MEDLINE]
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