Expression of the α₂-macroglobulin-encoding gene in rat brain and cultured astrocytes

The α₂-macroglobulin (α₂M), a protease inhibitor, is a major acute-phase protein in rats, and is produced in the liver during acute inflammation. Recently, it has been demonstrated that α₂M is also produced by cultured astrocytes from newborn rat brain and has neurite-promoting activity. Here, we found that the expression of the α ₂M gene was significantly enhanced in the brain following intraperitoneal injection of the neurotoxicant, kainic acid (KA), suggesting that α₂M acts as an acute-phase protein in the brain, as in the case of the liver, and may be involved in neural repair processes. Expression of α₂M in cultured astrocytes was shown to be stimulated by interleukin-6 (IL-6) and/or leukemia inhibitory factor (LIF) in the presence of glucocorticoid. The amount of mRNAs for IL-6 and LIF increased in the brain of KA-injected rats prior to α₂M induction. These results strongly suggested that IL-6 and LIF are involved in α₂M induction in the brain, as in the case of the liver. Analysis of the cis-acting element(s) and the trans-acting factor(s) suggested that the regulatory mechanism for α₂M expression in astrocytes was similar to that in inflamed liver.