Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver |
| |
Authors: | D Maione E Di Carlo W Li P Musiani A Modesti M Peters S Rose-John C Della Rocca M Tripodi D Lazzaro R Taub R Savino G Ciliberto |
| |
Affiliation: | Istituto Ricerche di Biologia Molecolare (IRBM) P.Angeletti, Via Pontina Km 30.600, 00400 Pomezia, Rome. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|