Liver failure and defective hepatocyte regeneration in interleukin-6- deficient mice

Drew E. Cressman, Linda E. Greenbaum, Robert A. DeAngelis, Gennaro Ciliberto, Emma E. Furth, Valeria Poli, Rebecca Taub

Research output: Contribution to journalArticle

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Abstract

Liver regeneration stimulated by a loss of liver mass leads to hepatocyte and nonparenchymal cell proliferation and rapid restoration of liver parenchyma. Mice with targeted disruption of the interleukin-6 (IL-6) gene had impaired liver regeneration characterized by liver necrosis and failure. There was a blunted DNA synthetic response in hepatocytes of these mice but not in nonparenchymal liver cells. Furthermore, there were discrete G1 phase (prereplicative stage in the cell cycle) abnormalities including absence of STAT3 (signal transducer and activator of transcription protein 3) activation and depressed AP-1, Myc, and cyclin D1 expression. Treatment of IL-6-deficient mice with a single preoperative dose of IL-6 returned STAT3 binding, gene expression, and hepatocyte proliferation to near normal and prevented liver damage, establishing that IL-6 is a critical component of the regenerative response.

Original languageEnglish
Pages (from-to)1379-1383
Number of pages5
JournalScience
Volume274
Issue number5291
DOIs
Publication statusPublished - Nov 22 1996

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Liver Failure
Regeneration
Hepatocytes
STAT Transcription Factors
STAT3 Transcription Factor
Interleukin-6
Liver Regeneration
Liver
Cyclin D1
Transcription Factor AP-1
G1 Phase
Protein Binding
Cell Cycle
Necrosis
Cell Proliferation
Gene Expression
mouse interleukin-6
DNA
Genes
enhancer-binding protein AP-3

ASJC Scopus subject areas

  • General

Cite this

Cressman, D. E., Greenbaum, L. E., DeAngelis, R. A., Ciliberto, G., Furth, E. E., Poli, V., & Taub, R. (1996). Liver failure and defective hepatocyte regeneration in interleukin-6- deficient mice. Science, 274(5291), 1379-1383. https://doi.org/10.1126/science.274.5291.1379

Liver failure and defective hepatocyte regeneration in interleukin-6- deficient mice. / Cressman, Drew E.; Greenbaum, Linda E.; DeAngelis, Robert A.; Ciliberto, Gennaro; Furth, Emma E.; Poli, Valeria; Taub, Rebecca.

In: Science, Vol. 274, No. 5291, 22.11.1996, p. 1379-1383.

Research output: Contribution to journalArticle

Cressman, DE, Greenbaum, LE, DeAngelis, RA, Ciliberto, G, Furth, EE, Poli, V & Taub, R 1996, 'Liver failure and defective hepatocyte regeneration in interleukin-6- deficient mice', Science, vol. 274, no. 5291, pp. 1379-1383. https://doi.org/10.1126/science.274.5291.1379
Cressman DE, Greenbaum LE, DeAngelis RA, Ciliberto G, Furth EE, Poli V et al. Liver failure and defective hepatocyte regeneration in interleukin-6- deficient mice. Science. 1996 Nov 22;274(5291):1379-1383. https://doi.org/10.1126/science.274.5291.1379
Cressman, Drew E. ; Greenbaum, Linda E. ; DeAngelis, Robert A. ; Ciliberto, Gennaro ; Furth, Emma E. ; Poli, Valeria ; Taub, Rebecca. / Liver failure and defective hepatocyte regeneration in interleukin-6- deficient mice. In: Science. 1996 ; Vol. 274, No. 5291. pp. 1379-1383.
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