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

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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

Adenoma
Liver
Hyperplasia
Interleukin-6
Hepatocytes
Interleukin-6 Receptors
Myeloproliferative Disorders
Tumor Necrosis Factor Receptors
Hepatectomy
Bioactivity
Transgenic Mice
Tumor Necrosis Factor-alpha
Cytokines

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver. / Maione, Domenico; Di Carlo, Emma; Li, Wei; Musiani, Piero; Modesti, Andrea; Peters, Malte; Rose-John, Stefan; Della Rocca, Carlo; Tripodi, Marco; Lazzaro, Domenico; Taub, Rebecca; Savino, Rocco; Ciliberto, Gennaro.

In: EMBO Journal, Vol. 17, No. 19, 01.10.1998, p. 5588-5597.

Research output: Contribution to journalArticle

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, vol. 17, no. 19, pp. 5588-5597. https://doi.org/10.1093/emboj/17.19.5588
Maione, Domenico ; Di Carlo, Emma ; Li, Wei ; Musiani, Piero ; Modesti, Andrea ; Peters, Malte ; Rose-John, Stefan ; Della Rocca, Carlo ; Tripodi, Marco ; Lazzaro, Domenico ; Taub, Rebecca ; Savino, Rocco ; Ciliberto, Gennaro. / Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver. In: EMBO Journal. 1998 ; Vol. 17, No. 19. pp. 5588-5597.
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