Tissue inhibitor of metalloproteinases (TIMP-1) stimulates the secretion of collagenase from human skin fibroblasts

Biochem Biophys Res Commun. 1994 Sep 15;203(2):874-80. doi: 10.1006/bbrc.1994.2264.

Abstract

This study aimed to investigate possible feedback mechanisms in the control of collagenase (matrix metalloproteinase-1) and tissue inhibitor of metalloproteinases (TIMP-1). Procollagenase, active collagenase, TIMP-1 and collagenase-TIMP complex were applied to human skin and synovial fibroblasts for 48 hours, the cells were washed and the resulting collagenase and TIMP-1 secretion was measured over the following 72 hours using ELISAs. Of the additions, only TIMP-1 showed any measurable effect, stimulating collagenase secretion over a range of 1-8 micrograms/ml. Endotoxin contamination was ruled out as an explanation and the active conformation of the TIMP-1 molecule was shown to be necessary.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Collagenases / metabolism*
  • Collagenases / pharmacology
  • Dose-Response Relationship, Drug
  • Endotoxins / analysis
  • Enzyme Precursors / pharmacology
  • Feedback
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology*
  • Glycoproteins / administration & dosage
  • Glycoproteins / pharmacology*
  • Humans
  • Interleukin-1 / pharmacology
  • Skin / enzymology*
  • Tissue Inhibitor of Metalloproteinases

Substances

  • Endotoxins
  • Enzyme Precursors
  • Glycoproteins
  • Interleukin-1
  • Tissue Inhibitor of Metalloproteinases
  • Collagenases
  • procollagenase