IL-6 upregulates its own receptor on some human myeloma cell lines

Cytokine. 2001 Jun 21;14(6):352-6. doi: 10.1006/cyto.2001.0911.

Abstract

Interleukin 6 (IL-6) is the major survival factor of myeloma cells. In this study, we demonstrate that IL-6, oncostatin M (OSM) and leukemia inhibitory factor (LIF) upregulate membrane IL-6 receptor alpha (IL-6Ralpha) on OPM-2 myeloma cell line at transcriptional level. In OPM-2 cells, IL-6, OSM and LIF induce both signal transducers and activators of transcription (STAT), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI 3-K) activation. We show that the cytokine-induced upregulation of IL-6Ralpha can be abolished by a janus kinase (JAK)-2 specific inhibitor, i.e. AG490, suggesting an involvement of the JAK/STAT pathway in this process. Finally, IL-6Ralpha upregulation was also inhibited by wortmannin, an inhibitor of the PI 3-kinase pathway. In conclusion, IL-6 can upregulate its own receptor on OPM-2 cells probably through the JAK/STAT and PI 3-kinase pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Antibodies, Monoclonal / metabolism
  • Blotting, Northern
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Flow Cytometry
  • Growth Inhibitors / metabolism
  • Humans
  • Immunoblotting
  • Interleukin-6 / metabolism*
  • Janus Kinase 2
  • Leukemia Inhibitory Factor
  • Lymphokines / metabolism
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinases
  • Multiple Myeloma / metabolism*
  • Oncostatin M
  • Peptides / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Proto-Oncogene Proteins*
  • Receptors, Interleukin-6 / metabolism*
  • Signal Transduction
  • Tyrphostins / pharmacology
  • Up-Regulation*
  • Wortmannin

Substances

  • Androstadienes
  • Antibodies, Monoclonal
  • Enzyme Inhibitors
  • Flavonoids
  • Growth Inhibitors
  • Interleukin-6
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • Lymphokines
  • OSM protein, human
  • Peptides
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Receptors, Interleukin-6
  • Tyrphostins
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
  • Oncostatin M
  • Protein-Tyrosine Kinases
  • JAK2 protein, human
  • Janus Kinase 2
  • Mitogen-Activated Protein Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Wortmannin