Cytokines oncostatin M and interleukin 1 regulate the expression of the IL-6 receptor (gp80, gp130).
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)
Geisterfer
M
M
Department of Pathology, McMaster University, Hamilton, Canada.
Richards
C D
CD
Gauldie
J
J
D000209:Acute-Phase Proteins / Q000187:drug effects; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018123:Receptors, Interleukin / Q000235:genetics*; D019947:Receptors, Interleukin-6; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D015703:Antigens, CD; D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D010455:Peptides; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D053683:Oncostatin M; D003907:Dexamethasone