Cytokines oncostatin M and interleukin 1 regulate the expression of the IL-6 receptor (gp80, gp130)

Cytokine. 1995 Aug;7(6):503-9. doi: 10.1006/cyto.1995.0068.

Abstract

The steady-state mRNA levels of the interleukin 6 receptor (IL-6R, gp80) and its signal transducing molecule, gp130, were examined in the rat hepatoma cell line, H-35, stimulated by cytokines IL-6, IL-1, oncostatin M (OSM) and/or Dexamethasone (Dex). In contrast to our previous findings in vivo [Geisterfer et al., 1993, Cytokine, 5:1] in vitro Dex seemed to be the major stimulator of IL-6R mRNA expression, whereas IL-6 seemed to have little effect on the expression of its own receptor mRNA levels. However, the presence of other cytokines influenced the Dex mediated stimulation of IL-6R expression. OSM stimulated IL-6R mRNA levels. At 6 h, cells stimulated with OSM showed a 2.1-fold increase in IL-6R mRNA expression. This stimulation was additive with the Dex-mediated stimulation of IL-6R mRNA levels. In contrast, IL-1 inhibited the Dex-mediated stimulation of IL-6R mRNA. At the same time, IL-1 stimulated the presence of a second smaller mRNA transcript. This mRNA species contained the extracellular domain but lacked both the transmembrane and cytoplasmic domains of the IL-6R, suggesting alternate splicing, possibly coding for a soluble form of gp80. Unlike the gp80 IL-6R molecule, the expression of the gp130 molecule normally expressed as two species of mRNA was not regulated to any major extent in vitro. IL-1 and OSM stimulated both mRNA bands (7.5 and 9.0 kb) approximately 2-fold, whereas IL-6 stimulated mainly the upper 9.0 kb mRNA band.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / drug effects
  • Animals
  • Antigens, CD / genetics*
  • Antineoplastic Agents / pharmacology*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Cytokines / pharmacology*
  • Dexamethasone / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Interleukin-1 / pharmacology*
  • Interleukin-6 / pharmacology
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / metabolism
  • Oncostatin M
  • Peptides / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Interleukin / genetics*
  • Receptors, Interleukin-6
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Tumor Cells, Cultured

Substances

  • Acute-Phase Proteins
  • Antigens, CD
  • Antineoplastic Agents
  • Cysteine Proteinase Inhibitors
  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Peptides
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-6
  • Oncostatin M
  • Dexamethasone