PROTEIN SYNTHESIS-DEPENDENT INDUCTION OF INTERLEUKIN-1-BETA BY LIPOPOLYSACCHARIDE IS INHIBITED BY DEXAMETHASONE VIA MESSENGER-RNA DESTABILIZATION IN HUMAN ASTROGLIAL CELLS

Dexamethasone inhibits lipopolysaccharide-induced synthesis of the cyt okine, interleukin-1 beta, in cerebrospinal fluid of patients with bac terial meningitis. Along with monocytes, astrocytes are capable of pro ducing lipopolysaccharide-induced interleukin-1 beta in the central ne rvous system. The objective of this study was to investigate the induc tion of interleukin-1 beta mRNA by lipopolysaccharide, and the inhibit ion of this process by dexamethasone, in human astrocytes using the as trocytoma cell line U-373MG as a model system. Dexamethasone-mediated inhibition of induction of interleukin-1 beta mRNA by lipopolysacchari de required a functional glucocorticoid receptor. In contrast to monoc ytes, lipopolysaccharide induction of interleukin-1 beta mRNA in U-373 MG cells required de novo protein synthesis. Dexamethasone also had no effect on lipopolysaccharide-induced interleukin-1 beta transcription al initiation in U-373MG cells. U-373MG cells were similar to monocyte s, however, with respect to the ability of dexamethasone to decrease i nterleukin-1 beta mRNA half-life. These findings demonstrate that the mode of lipopolysaccharide induction of interleukin-1 beta mRNA, and i nhibition of this process by dexamethasone, can vary in different cell types.