Modulation of the gene network connected to interferon-gamma in liver regeneration from oval cells

Am J Pathol. 1999 Oct;155(4):1075-85. doi: 10.1016/s0002-9440(10)65210-8.


Suppression subtractive hybridization was used to clone genes associated with proliferation of oval cells in rat liver regenerating after a 70% partial hepatectomy combined with the feeding of 2-acetylaminofluorene. A subset of the identified genes comprised interferon-gamma receptor alpha subunit (IFN-gammaRalpha), gp91phox, interleukin-1beta (IL-1beta), lymphocyte function-associated molecule-1alpha (LFA-1), eukaryotic initiation factor-2-associated 67-kd protein (eIF-2-associated 67-kd protein), and alpha-fetoprotein, which constitute part of the cellular program modulated by IFN-gamma. Therefore, expression analysis performed by Northern blotting and immunohistochemistry were extended to include IFN-gamma, the IFN-gamma receptor beta subunit (IFN-gammaRbeta), three secondary response genes induced by interaction of IFN-gamma with IFN-gamma receptor complexes, ie, IL-1beta-converting enzyme (ICE), intercellular adhesion molecule-1 (ICAM-1), and urokinase-type plasminogen activator receptor (uPAR), and a cytokine inducing IFN-gamma expression, ie, interleukin-18 (IL-18). The Northern blot analysis showed that all examined genes were modulated when progenitor-like oval cells were activated and recruited for liver regeneration. Immunohistochemistry localized the subunits of the IFN-gamma receptor complex, IFN-gammaRalpha and IFN-gammaRbeta, the secondary response genes uPAR and ICAM-1, the IFN-gamma-inducing factor IL-18, and ICE to the ductular structures of oval cells. In contrast, during liver regeneration after a 70% partial hepatectomy, only modulation of IL-1beta and ICE was observed. Our results, therefore, indicate that IFN-gamma-mediated events may be particularly important when cells in the bile ductules must respond to liver damage by production of ductular oval cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 2-Acetylaminofluorene
  • Animals
  • Bile Ducts / cytology
  • Bile Ducts / metabolism*
  • Blotting, Northern
  • Caspase 1 / biosynthesis
  • Cell Division / genetics
  • Epithelial Cells / metabolism
  • Gene Expression Regulation*
  • Hepatectomy
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics*
  • Interferon-gamma / physiology
  • Interleukin-18 / biosynthesis
  • Liver / cytology
  • Liver / metabolism*
  • Liver Regeneration / genetics*
  • Liver Regeneration / physiology
  • Male
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred F344
  • Receptors, Interferon / biosynthesis
  • Signal Transduction / genetics


  • Interleukin-18
  • RNA, Messenger
  • Receptors, Interferon
  • interferon gamma receptor
  • Interferon-gamma
  • 2-Acetylaminofluorene
  • Caspase 1