Epidermal Growth Factor Regulates Astrocyte Expression of the Interleukin-4 Receptor via a MAPK-Independent Pathway

• Published in: Cellular immunology 2001-02, Vol.208 (1), p.18-24
• Main Authors: Barna, B.P., Mattera, R., Jacobs, B.S., Drazba, J., Estes, M.E., Prayson, R.A., Barnett, G.H.
• Format: Article
• Language: English
• Subjects: astrocytes; Astrocytes - cytology; Astrocytes - drug effects; Astrocytes - metabolism; Blotting, Western; Cells, Cultured; DNA - biosynthesis; EGF; Enzyme Activation - drug effects; Epidermal Growth Factor - antagonists & inhibitors; Epidermal Growth Factor - pharmacology; Flavonoids - pharmacology; Gene Expression Regulation - drug effects; human; Humans; IL-4; Interleukin-4 - pharmacology; Isoenzymes - antagonists & inhibitors; Isoenzymes - metabolism; MAPK; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; receptors; Receptors, Interleukin-4 - biosynthesis; Receptors, Interleukin-4 - genetics; Receptors, Interleukin-4 - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - drug effects; Time Factors; Tumor Cells, Cultured
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1006/cimm.2001.1768

Human astrocytes express the interleukin (IL)-4 receptor alpha chain (IL-4Rα) in vitro and in vivo but mechanisms governing astrocyte IL-4Rα expression have not been established. We hypothesized that epidermal growth factor (EGF) and IL-4, agents that profoundly affect astrocyte proliferation, might also alter IL-4Rα expression. Exposure to EGF for 24 h enhanced IL-4Rα mRNA levels; in contrast, IL-4 yielded no increase. Immunoblotting demonstrated that EGF but not IL-4 increased astrocyte IL-4Rα protein after 2–4 days of exposure. Similarly, EGF but not IL-4 strongly activated phosphorylation of p42/p44 extracellular regulated kinase isoforms, a reaction blocked by the mitogen-activated protein kinase (MAPK) inhibitor, PD98059. PD98059 also blocked EGF-stimulated DNA synthesis but not IL-4Rα mRNA levels, while antibody to the EGF receptor (erbB1) blocked both EGF effects. Data suggest that astrocyte IL-4Rα expression is upregulated by EGF but not by IL-4 in an EGF-receptor-dependent manner and that mechanisms are independent of MAPK activation.