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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokines / metabolism
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Hypergammaglobulinemia / immunology*
  • Immunity, Innate / genetics
  • Inflammation Mediators / metabolism
  • Leukocytes / immunology*
  • Lipopolysaccharides / immunology
  • Matrix Metalloproteinases, Membrane-Associated / genetics
  • Matrix Metalloproteinases, Membrane-Associated / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Protein Binding
  • Signal Transduction


  • Cytokines
  • GPI-Linked Proteins
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Matrix Metalloproteinases, Membrane-Associated
  • matrix metalloproteinase 25