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RESEARCH PRODUCT
Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver
Piero MusianiEmma Di CarloRocco SavinoGennaro CilibertoRebecca TaubMarco TripodiDomenico MaioneAndrea ModestiWei LiCarlo Della RoccaDomenico LazzaroStefan Rose JohnMalte Peterssubject
AdenomaSTAT3 Transcription FactorAdenomail-6; liver adenomas; nodular hyperplasia; soluble il-6rMice TransgenicBiologyGeneral Biochemistry Genetics and Molecular BiologyProto-Oncogene Proteins c-mycMiceMyeloproliferative Disordersil-6medicineAnimalsnodular hyperplasiaReceptorMolecular BiologyHyperplasialiver adenomasHaptoglobinsGeneral Immunology and MicrobiologyInterleukin-6General NeuroscienceLiver NeoplasmsHyperplasiaGlycoprotein 130medicine.diseaseReceptors Interleukin-6Liver regenerationLiver RegenerationDNA-Binding Proteinsmedicine.anatomical_structureGene Expression RegulationLiverSolubilityHepatocyteTrans-ActivatorsCancer researchEndothelium Vascularsoluble il-6rNodular regenerative hyperplasiaResearch Articledescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1998-10-01 | The EMBO Journal |