Activation of corneal fibroblast-derived matrix metalloproteinase-2 by tryptase

Curr Eye Res. 2006 Apr;31(4):313-7. doi: 10.1080/02713680600629789.

Abstract

Purpose: The presence of the active form of matrix metalloproteinase (MMP)-2 and an increased concentration of tryptase are characteristics of tear fluid of individuals with vernal keratoconjunctivitis. Although tryptase does not mediate the activation of purified MMP-2, we have now examined whether it might activate MMP-2 in the presence of cultured human corneal fibroblasts.

Methods: Corneal fibroblasts were cultured in the absence or presence of tryptase, and the activation status of MMP-2 was determined by gelatin zymography.

Results: MMP-2 released from corneal fibroblasts was activated by exogenous tryptase. This effect was not mediated by protease-activated receptor 2 or the plasmin-plasminogen system, and it was not apparent on incubation of tryptase with medium conditioned by corneal fibroblasts. It was inhibited by tissue inhibitor of metalloproteinase (TIMP)-2 but not by TIMP-1.

Conclusions: Tryptase activates MMP-2 released from corneal fibroblasts. This action requires the presence of the cells themselves and might be responsible for the presence of activated MMP-2 in tear fluid of individuals with vernal keratoconjunctivitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Corneal Stroma / cytology
  • Corneal Stroma / drug effects*
  • Corneal Stroma / enzymology
  • Enzyme Activation
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / pharmacology
  • Plasminogen Activator Inhibitor 2 / pharmacology
  • Serine Endopeptidases / pharmacology*
  • Tissue Inhibitor of Metalloproteinase-2 / pharmacology
  • Tryptases

Substances

  • Plasminogen Activator Inhibitor 1
  • Plasminogen Activator Inhibitor 2
  • Tissue Inhibitor of Metalloproteinase-2
  • Serine Endopeptidases
  • Tryptases
  • Matrix Metalloproteinase 2