Protein synthesis-dependent induction of interleukin-1β by lipopolysaccharide is inhibited by dexamethasone via mRNA destabilization in human astroglial cells

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Abstract
Dexamethasone inhibits lipopolysaccharide-induced synthesis of the cytokine, interleukin-1β, in cerebrospinal fluid of patients with bacterial meningitis. Along with monocytes, astrocytes are capable of producing lipopolysaccharide-induced interleukin-1β in the central nervous system. The objective of this study was to investigate the induction of interleukin-1β mRNA by lipopolysaccharide, and the inhibition of this process by dexamethasone, in human astrocytes using the astrocytoma cell line U-373MG as a model system. Dexamethasone-mediated inhibition of induction of interleukin-1β mRNA by lipopolysaccharide required a functional glucocorticoid receptor. In contrast to monocytes, lipopolysaccharide induction of interleukin-1β mRNA in U-373MG cells requiredde novo protein synthesis. Dexamethasone also had no effect on lipopolysaccharide-induced interleukin-1β transcriptional initiation in U-373MG cells. U-373MG cells were similar to monocytes, however, with respect to the ability of dexamethasone to decrease interleukin-1β mRNA half-life. These findings demonstrate that the mode of lipopolysaccharide induction of interleukin-1β mRNA, and inhibition of this process by dexa-methasone, can vary in different cell types.