Synthesis of tissue inhibitor of metalloproteinase-1 (TIMP-1) in human hepatoma cells (HepG2). Up-regulation by interleukin-6 and transforming growth factor beta 1

FEBS Lett. 1992 Nov 23;313(2):143-7. doi: 10.1016/0014-5793(92)81431-k.


Metalloproteinases and their specific inhibitors, believed to play a role in extracellular matrix metabolism, are regulated by inflammatory cytokines. Here we have addressed the question of whether liver, the major site of synthesis of plasma proteinase inhibitors, is also capable of synthesizing the tissue inhibitor of metalloproteinase-1 (TIMP-1). We show at mRNA and protein levels that TIMP-1 is expressed in differentiated human hepatoma cells (HepG2) and that its synthesis is up-regulated by interleukin-6 (IL-6), transforming growth factor beta 1 and phorbol 12-myristate 13-acetate. The physiological role of this phenomenon is underlined by the fact that lipopolysaccharide administration into rats in vivo, as well as IL-6-stimulation of rat hepatocytes in primary culture, also leads to an increase of TIMP-1 mRNA in liver cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / metabolism*
  • Glycoproteins / biosynthesis*
  • Humans
  • Interleukin-6 / pharmacology*
  • Lipopolysaccharides
  • Liver Neoplasms / metabolism*
  • Metalloendopeptidases / antagonists & inhibitors*
  • Tissue Inhibitor of Metalloproteinases
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured
  • Up-Regulation


  • Glycoproteins
  • Interleukin-6
  • Lipopolysaccharides
  • Tissue Inhibitor of Metalloproteinases
  • Transforming Growth Factor beta
  • Metalloendopeptidases