Protein synthesis-dependent induction of interleukin-1 beta by lipopolysaccharide is inhibited by dexamethasone via mRNA destabilization in human astroglial cells.
Dexamethasone inhibits lipopolysaccharide-induced synthesis of the cytokine, interleukin-1 beta, in cerebrospinal fluid of patients with bacterial meningitis. Along with monocytes, astrocytes are capable of producing lipopolysaccharide-induced interleukin-1 beta in the central nervous system. The objective of this study was to investigate the induction of interleukin-1 beta 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 beta mRNA by lipopolysaccharide required a functional glucocorticoid receptor. In contrast to monocytes, lipopolysaccharide induction of interleukin-1 beta mRNA in U-373MG cells required de novo protein synthesis. Dexamethasone also had no effect on lipopolysaccharide-induced interleukin-1 beta 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 beta mRNA half-life. These findings demonstrate that the mode of lipopolysaccharide induction of interleukin-1 beta mRNA, and inhibition of this process by dexamethasone, can vary in different cell types.
Kimberlin
D W
DW
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063, USA.
Willis
S A
SA
McCracken
G H
GH
Nisen
P D
PD
D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001254:Astrocytoma / Q000276:immunology; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D015735:Mifepristone / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D015735:Mifepristone; D003907:Dexamethasone; D003513:Cycloheximide