A cytokine-selective defect in interleukin-1β-mediated acute phase gene expression in a subclone of the human hepatoma cell line (HepG2)

D. H. Perlmutter, H. R. Colten, S. P. Adams, L. T. May, P. B. Sehgal, R. J. Fallon

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Several well-differentiated human hepatoma cell lines (HepG2, Hep3B) have been used to identify factors which regulate hepatic gene expression during the host response to inflammation/tissue injury (acute phase response). Studies in these cell lines, as well as in primary cultures of rat, rabbit, and mouse hepatocytes, have demonstrated that interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), and interferon-β2 (IFN-β2) each mediate changes in expression of several hepatic acute phase genes. In this study we identify a subclone of the HepG2 cell line in which there is a selective defect in IL-1β-mediated acute phase gene expression. Recombinant human IL-1β mediates an increase in synthesis of the positive acute phase complement protein factor B and a decrease in synthesis of negative acute phase protein albumin in the parent uncloned HepG2 cell line (HG2Y), but not in the subclone HG2N. Recombinant human IFN-β2 and TNF-α, however, regulate acute phase protein synthesis in the subclone HG2N; i.e. IFN-β2 and TNF-α increase synthesis of factor B and decrease synthesis of albumin in both HG2Y and HG2N cells. Equilibrium binding analysis with 125I-rIL-1β at 4°C showed that both HG2N and HG2Y cells bind IL-1β specifically and saturably. HG2N and HG2Y possess 3.8 and 4.0 x 103 plasma membrane receptors/cell with affinities of 0.96 and 1.07 x 10-9 M, respectively. Thus, the defect in this subclone of the HepG2 cell line is likely to involve the signal transduction pathway for the biological activity of IL-1β and will be useful in elucidation of this signal transduction pathway.

Original languageEnglish (US)
Pages (from-to)7669-7674
Number of pages6
JournalJournal of Biological Chemistry
Volume264
Issue number13
StatePublished - 1989

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Perlmutter, D. H., Colten, H. R., Adams, S. P., May, L. T., Sehgal, P. B., & Fallon, R. J. (1989). A cytokine-selective defect in interleukin-1β-mediated acute phase gene expression in a subclone of the human hepatoma cell line (HepG2). Journal of Biological Chemistry, 264(13), 7669-7674.