Studies,vith tumor necrosis factor p55 reeeptor- 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.
Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver / D., Maione; E., Di Carlo; W., Li; P., Musiani; A., Modesti; M., Peters; S., Rose John; DELLA ROCCA, Carlo; Tripodi, Marco; D., Lazzaro; R., Taub; R., Savino; G., Ciliberto. - In: EMBO JOURNAL. - ISSN 0261-4189. - STAMPA. - 17:19(1998), pp. 5588-5597. [10.1093/emboj/17.19.5588]
Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver
DELLA ROCCA, Carlo;TRIPODI, Marco;
1998
Abstract
Studies,vith tumor necrosis factor p55 reeeptor- 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.