EXPRESSION OF THE ALPHA(2)-MACROGLOBULIN-ENCODING GENE IN RAT-BRAIN AND CULTURED ASTROCYTES

The alpha(2)-macroglobulin (alpha(2)M), a protease inhibitor, is a maj or acute-phase protein in rats, and is produced in the liver during ac ute inflammation. Recently, it has been demonstrated that alpha(2)M is also produced by cultured astrocytes from newborn rat brain and has n eurite-promoting activity. Here, we found that the expression of the a lpha(2)M gene was significantly enhanced in the brain following intrap eritoneal injection of the neurotoxicant, kainic acid (KA), suggesting that alpha(2)M acts as an acute-phase protein in the brain, as in the case of the liver, and may be involved in neural repair processes. Ex pression of alpha(2)M in cultured astrocytes was shown to be stimulate d by interleukin-6 (IL-6) and/or leukemia inhibitory factor (LIF) in t he presence of glucocorticoid. The amount of mRNAs for IL-6 and LIF in creased in the brain of KA-injected rats prior to alpha(2)M induction. These results strongly suggested that IL-6 and LIF are involved in al pha(2)M 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 alpha(2)M expression in astrocytes w as similar to that in inflamed liver.