Modulation of murine and human interferon-gamma receptor expression by their ligands or phorbol ester

Cytokine. 1994 Jan;6(1):70-8. doi: 10.1016/1043-4666(94)90010-8.

Abstract

IFN-gamma receptor expression on murine leukaemic L1210-cells has been studied. With the help of a transfected cell-line expressing the heterologous human receptor it was possible to discern receptor-specific properties like internalization from those regulating their expression on the surface. Recombinant IFN-gamma binds specifically to its homologous receptor at 4 degrees C and is rapidly internalized at physiologic temperatures. For this effect to occur, ligand binding to its receptor at 37 degrees C is necessary and sufficient. This notion is confirmed since a reduction in the number of heterologous human IFN-gamma receptors on the murine cell surface occurred exclusively after treatment with human IFN-gamma. Even weak doses of ligand, insufficient to occupy all receptors, led to a pronounced disappearance of binding sites. However, both receptors are simultaneously up-regulated in the presence of TPA, indicating a separate pathway which is not species-specific. Our findings imply that similar elements of the intracellular signal transduction machinery are involved in the control of MuIFN-gamma and HuIFN-gamma receptor expression. The results indicate also that factors involved in binding, internalization, and regulation of receptor gene expression are not species-specific.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Down-Regulation / drug effects
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interferon-gamma / metabolism
  • Interferon-gamma / pharmacology*
  • Kinetics
  • Leukemia L1210 / immunology
  • Leukemia L1210 / metabolism
  • Mice
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Receptors, Interferon / biosynthesis*
  • Receptors, Interferon / metabolism
  • Recombinant Proteins
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Transfection
  • Up-Regulation / drug effects

Substances

  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Interferon
  • Recombinant Proteins
  • interferon gamma receptor
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate