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

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.