Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver

Domenico Maione, Emma Di Carlo, Wei Li, Piero Musiani, Andrea Modesti, Malte Peters, Stefan Rose-John, Carlo Della Rocca, Marco Tripodi, Domenico Lazzaro, Rebecca Taub, Rocco Savino, Gennaro Ciliberto

Research output: Contribution to journalArticle

Abstract

Studies with tumor necrosis factor p55 receptor- and interleukin-6 (IL-6)-deficient mice have shown that IL-6 is required for hepatocyte proliferation and reconstitution of the liver mass after partial hepatectomy. The biological activities of IL-6 are potentiated when this cytokine binds soluble forms of its specific receptor subunit (sIL-6R) and the resulting complex interacts with the transmembrane signaling chain gp130. We show here that double transgenic mice expressing high levels of both human IL-6 and sIL-6R under the control of liver-specific promoters spontaneously develop nodules of hepatocellular hyperplasia around periportal spaces and present signs of sustained hepatocyte proliferation. The resulting picture is identical to that of human nodular regenerative hyperplasia, a condition frequently associated with immunological and myeloproliferative disorders. In high expressors, hyperplastic lesions progress with time into discrete liver adenomas. These data strongly suggest that the IL-6/sIL-6R complex is both a primary stimulus to hepatocyte proliferation and a pathogenic factor of hepatocellular transformation.

Original languageEnglish
Pages (from-to)5588-5597
Number of pages10
JournalEMBO Journal
Volume17
Issue number19
DOIs
Publication statusPublished - Oct 1 1998

    Fingerprint

Keywords

  • IL-6
  • Liver adenomas
  • Nodular hyperplasia
  • Soluble IL-6R

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Maione, D., Di Carlo, E., Li, W., Musiani, P., Modesti, A., Peters, M., Rose-John, S., Della Rocca, C., Tripodi, M., Lazzaro, D., Taub, R., Savino, R., & Ciliberto, G. (1998). Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver. EMBO Journal, 17(19), 5588-5597. https://doi.org/10.1093/emboj/17.19.5588