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Pro-inflammatory effects of matrix metalloproteinase 7 in acute inflammation

R E Vandenbroucke1, I Vanlaere1, F Van Hauwermeiren1

  • 11] VIB Inflammation Research Center, Ghent, Belgium [2] Department of Biomedical Molecular Biology, University Ghent, Ghent, Belgium.

Mucosal Immunology
|October 17, 2013
PubMed

Insights

Matrix metalloproteinase 7 (MMP7) absence protects mice from lethal inflammation by reducing intestinal permeability and bacterial spread. MMP7-activated defensins may paradoxically promote inflammation, contributing to gut leakage.

Area of Science:

  • Immunology
  • Gastroenterology
  • Molecular Biology

Background:

  • Matrix metalloproteinase 7 (MMP7) activates antimicrobial peptides (α-defensins) in the small intestine.
  • Paneth cells produce α-defensins, crucial for innate immunity.

Purpose of the Study:

  • To investigate the role of MMP7 in lipopolysaccharide (LPS)-induced inflammation and lethality.
  • To explore the pro-inflammatory potential of MMP7-activated α-defensins.

Main Methods:

  • Comparison of LPS response in wild-type (MMP7+/+) and knockout (MMP7-/-) mice.
  • Analysis of intestinal permeability, bacterial translocation, cytokine levels, and gene expression.
  • In vitro assessment of α-defensin effects on macrophage IL-6 release.

Main Results:

  • MMP7-/- mice showed resistance to LPS-induced lethality, reduced systemic cytokines, and decreased intestinal inflammation.
  • LPS induced MMP7 activation, Paneth cell degranulation, and intestinal permeability in MMP7+/+ mice.
  • MMP7 absence reduced LPS-induced intestinal permeability and bacterial translocation.

Conclusions:

  • Absence of MMP7 confers protection against LPS-induced intestinal permeability and lethality.
  • MMP7-activated α-defensins may possess pro-inflammatory activities, amplifying gut inflammation and leakage.

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