Regulation of gene expression by interleukin-6 in fetal rat hepatocyte primary cultures: Role of epidermal growth factor and dexamethasone

✍ Scribed by Cesar Roncero; Isabel Fabregat; Dr Manuel Benito

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 901 KB
• Volume: 22
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840220624

✦ Synopsis

Fetal rat hepatocytes incubated in the absence of hormonal signals, or under proliferative (presence of epidermal growth factor [EGF]) or differentiative (presence of dexamethasone) culture conditions, showed responsiveness to interleukin-6 (IL-6). Northern blotting analysis for some typical acute phase genes such as haptoglobin and other proteins not previously identified as acute-phase reactants, such as a-fetoprotein, &-microglobulin, and fibronectin, showed a positive modulation by IL-6, in a dose-dependent manner. However, a wellcharacterized negative acute-phase reactant such as al- bumin was not responsive to IL-6. The well-established synergism between glucocorticoids and IL-6 on inducing transcription is absent in fetal hepatocytes. Conversely, the combination of IL-6 and EGF produced different patterns of expression, depending on the messenger RNA (mRNA) analyzed. Thus, EGF abolished the increased mRNA levels of haptoglobin caused by IL-6 but had no effect on other genes such as a-fetoprotein and fibronectin. (HJ~PATOLOGY 1995;22:1769-1775.)

During development of higher eukaryotes, the tissuespecific and temporal expression of many genes is determined at transcription level. Combinations of growth factors, hormones, and cytokines control the expression of transcription factors that bind to specific DNA recognition sites within promoter and enhancer regions of the target genes. Transcription factors implicated in the regulation of tissue-specific gene expression are themselves submitted to different modes of regulation and are often expressed in a cell-type-specific manner.',' Culture of hepatocytes is a good model to study tissue-specific gene expression, because spe-Abbreviations: EQF, epidermal growth factor; IL-6, interleukin-6; SDS, sodium dodecyl sulfate; mRNA, messenger RNA.

From the Departamento de Bioqufmica y Biolosa Molecular 11, Centro