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

David W. Kimberlin, Susan A. Willis, George H. McCracken, Perry D. Nisen

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)199-204
Number of pages6
JournalJournal of Clinical Immunology
Volume15
Issue number4
DOIs
StatePublished - Jul 1 1995

Keywords

  • Interleukin-1
  • gene expression
  • meningitis
  • steroids
  • transcription

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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