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 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 alpha-fetoprotein, beta 2-microglobulin, and fibronectin, showed a positive modulation by IL-6, in a dose-dependent manner. However, a well-characterized 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. 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 alpha-fetoprotein and fibronectin.
D000418:Albumins / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005353:Fibronectins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D016259:Genes, myc; D006242:Haptoglobins / Q000235:genetics; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000196:embryology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000509:alpha-Fetoproteins / Q000235:genetics; D001613:beta 2-Microglobulin / Q000235:genetics
D000418:Albumins; D005353:Fibronectins; D006242:Haptoglobins; D015850:Interleukin-6; D012333:RNA, Messenger; D000509:alpha-Fetoproteins; D001613:beta 2-Microglobulin; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D004247:DNA