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Coexpression of IL‐6 and soluble IL‐6R causes nodular regenerative hyperplasia and adenomas of the liver
Author(s) -
Maione Domenico,
Di Carlo Emma,
Li Wei,
Musiani Piero,
Modesti Andrea,
Peters Malte,
RoseJohn Stefan,
Rocca Carlo Della,
Tripodi Marco,
Lazzaro Domenico,
Taub Rebecca,
Savino Rocco,
Ciliberto Gennaro
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.19.5588
Subject(s) - biology , nodular regenerative hyperplasia , focal nodular hyperplasia , hyperplasia , pathology , cancer research , medicine , endocrinology , cirrhosis , hepatocellular carcinoma , portal hypertension
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.