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-4R alpha) in vitro and in vivo but mechanisms governing astrocyte IL-4R alpha expression have not been established. We hypothesized that epidermal growt h factor (EGF) and IL-4, agents that profoundly affect astrocyte proliferat ion, might also alter IL-4R alpha expression. Exposure to EGF for 24 h enha nced IL-4R alpha mRNA levels; in contrast, IL-4 yielded no increase. Immuno blotting demonstrated that EGF but not IL-4 increased astrocyte IL-4R alpha protein after 2-4 days of exposure. Similarly, EGF but not IL-4 strongly a ctivated phosphorylation of p42/p44 extracellular regulated kinase isoforms , a reaction blocked by the mitogen-activated protein kinase (MAPK) inhibit or, PD98059. PD98059 also blocked EGF-stimulated DNA synthesis but not IL-4 R alpha mRNA levels, while antibody to the EGF receptor (erbB1) blocked bot h EGF effects. Data suggest that astrocyte IL-4R alpha expression is upregu lated by EGF but not by IL-4 in an EGF-receptor-dependent manner and that m echanisms are independent of MAPK activation. (C) 2001 Academic Press.