Activation of corneal fibroblast-derived matrix metalloproteinase-2 by tryptase.
OBJECTIVE
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.
Yamamoto
Kazutaka
K
Department of Biomolecular Recognition and Ophthalmology, Yamaguchi University School of Medicine, Ube City, Yamaguchi, Japan.
Kumagai
Naoki
N
Fukuda
Ken
K
Fujitsu
Youichiro
Y
Nishida
Teruo
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003319:Corneal Stroma / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000494:pharmacology; D017396:Plasminogen Activator Inhibitor 2 / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000494:pharmacology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology; D053802:Tryptases
D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D019716:Tissue Inhibitor of Metalloproteinase-2; D012697:Serine Endopeptidases; D053802:Tryptases; D020778:Matrix Metalloproteinase 2