Soluble interleukin-6 receptor enhanced by oncostatin M induces major changes in gene expression profile of human hepatoma cells

Marianna Csilla Holub, Hargita Hegyesi, Peter Igaz, Anna Polgár, Sara Toth, Andras Falus

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Interleukin-6 (IL-6) binds to a receptor complex consisting of an 80 kDa binding unit (IL-6R) and gp130 responsible for signal transduction. Due to alternative splicing and/or proteolytic digestion IL-6R occurs in soluble form (sIL-6R), as well. Soluble IL-6R is able to bind to gp130 expressing on nucleated cells, thus sIL-6R makes most cells responsive to IL-6. In this study we found that oncostatin M (OSM), an other gp130 dependent cytokine with proliferation inhibitory potential, increases the expression of both membrane-bound IL-6R and sIL-6R generated by alternative splicing in hepatic and mammary carcinoma cell lines. Furthermore, we studied the functional relevance of the presence and binding of soluble IL-6R to HepG2 cells. Using a cDNA expression array, mRNA levels of about 580 human genes were tested by differential display analysis. Our findings suggest, that elevation of surface density of IL-6R by attachment of sIL-6R induces major modulation in gene expression profile of the hepatoma cells. Soluble IL-6R alone has minor effect, it rather decreases expression of some genes, while incubation with IL-6 and sIL-6R together induces major changes in the mRNA pattern of HepG2 cells. These data strongly suggest that presence and binding of soluble cytokine receptors are important elements of inter-cytokine cross talk and affects actual gene expression profile of responding cells.

Original languageEnglish
Pages (from-to)79-84
Number of pages6
JournalImmunology letters
Volume82
Issue number1-2
DOIs
Publication statusPublished - Jun 3 2002

Keywords

  • Cytokine
  • Gene expression profile
  • Interleukin-6 receptor
  • Macroarray
  • Oncostatin M
  • Soluble receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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