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 language||English (US)|
|Number of pages||6|
|Journal||Journal of Biological Chemistry|
|State||Published - 1989|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology