REGULATION OF GENE-EXPRESSION BY INTERLEUKIN-6 IN FETAL-RAT HEPATOCYTE PRIMARY CULTURES - ROLE OF EPIDERMAL GROWTH-FACTOR AND DEXAMETHASONE

Fetal rat hepatocytes incubated in the absence of hormonal signals, or under proliferative (presence of epidermal growth factor [EGF]) or di fferentiative (presence of dexamethasone) culture conditions, showed r esponsiveness 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 alpha-feto protein, beta(2)-microglobulin, and fibronectin, showed a positive mod ulation by IL-6, in a dose-dependent manner. However, a well-character ized negative acute-phase reactant such as albumin was not responsive to IL-6. The well-established synergism between glucocorticoids and IL -6 on inducing transcription is absent in fetal hepatocytes. Conversel y, the combination of IL-6 and EGF produced different patterns of expr ession, depending on the messenger RNA (mRNA) analyzed. Thus, EGF abol ished the increased mRNA levels of haptoglobin caused by IL-6 but had no effect on other genes such as Lu-fetoprotein and fibronectin.