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A novel role for matrix metalloproteinase-8 in sepsis

Patrick D Solan1, Katherine E Dunsmore, Alvin G Denenberg

  • 1Department of Surgery, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Cincinnati, OH, USA.

Critical Care Medicine
|October 25, 2011
PubMed
Abstract

Insights

Matrix metalloproteinase-8 (MMP-8) is linked to worse outcomes in pediatric septic shock. Inhibiting MMP-8 improved survival and reduced inflammation in a mouse model, suggesting it

Area of Science:

  • Pediatric critical care medicine
  • Immunology
  • Molecular biology

Background:

  • Matrix metalloproteinase-8 (MMP-8) mRNA expression is elevated in children with septic shock.
  • The role of MMP-8 in sepsis severity and inflammation remains unclear.

Purpose of the Study:

  • To investigate the association between MMP-8 and disease severity in pediatric septic shock.
  • To explore the therapeutic potential of MMP-8 inhibition in sepsis using a murine model.

Main Methods:

  • Retrospective analysis of pediatric septic shock patients (age ≤10 yrs).
  • Laboratory experiments using MMP-8 deficient and wild-type mice.
  • Assessment of MMP-8 mRNA, activity, organ failure, survival, and nuclear factor-κB activation.

Main Results:

  • Increased MMP-8 expression and activity in pediatric septic shock correlated with higher mortality and organ failure.
  • Genetic and pharmacologic MMP-8 inhibition improved survival and reduced inflammation in mice.
  • MMP-8 was identified as a direct activator of the pro-inflammatory transcription factor nuclear factor-κB.

Conclusions:

  • Matrix metalloproteinase-8 is a novel regulator of sepsis-induced inflammation.
  • MMP-8 represents a potential therapeutic target for sepsis management.

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