Soluble interleukin-6 receptor enhanced by oncostatin M induces major changes in gene expression profile of human hepatoma cells.
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.
Holub
Marianna Csilla
MC
Department of Genetics, Cell- and Immunobiology, Semmelweis University of Medicine, Budapest, Hungary.
Hegyesi
Hargita
H
Igaz
Peter
P
Polgár
Anna
A
Toth
Sara
S
Falus
Andras
A
D017398:Alternative Splicing; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D004357:Drug Synergism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000096:biosynthesis; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; C508351:OSM protein, human; D010455:Peptides; D012334:RNA, Neoplasm; D019947:Receptors, Interleukin-6; D053683:Oncostatin M