The hepatic interleukin-6 receptor. Down-regulation of the interleukin-6 binding subunit (gp80) by its ligand

FEBS Lett. 1992 Jul 20;306(2-3):219-22. doi: 10.1016/0014-5793(92)81004-6.


Interleukin-6 (IL6) exerts its action via a cell surface receptor composed of an 80 kDa IL6-binding protein (gp80) and a 130 kDa polypeptide involved in signal transduction (gp130). We studied the role of gp80 in binding, internalization and down-regulation of the hepatic IL6-receptor (IL6R) by its ligand in human hepatoma cells (HepG2). Comparison of transfected HepG2 cells overexpressing gp80 with parental cells indicate that gp80 is responsible for low affinity binding (Kd = 500 pM) of IL6. Furthermore, gp80 is rate-limiting in internalization and degradation of IL6. Internalization resulted in a rapid down-regulation (t1/2 approximately 15-30 min) of IL6-binding sites at the cell surface. More than 80% of the internalized [125I]rhIL6 was degraded. The reappearance of IL6-binding sites at the cell surface required greater than 8 h and was sensitive to cycloheximide, suggesting that gp80 is not recycled after internalization. The down-regulation of the hepatic IL6R by its ligand might play an important role as a protection against overstimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular
  • Down-Regulation*
  • Endocytosis
  • Humans
  • Interleukin-6 / metabolism*
  • Ligands
  • Liver / metabolism*
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / metabolism*
  • Receptors, Interleukin-6
  • Tumor Cells, Cultured


  • Interleukin-6
  • Ligands
  • Receptors, Immunologic
  • Receptors, Interleukin-6