Caspase-11 gene expression in response to lipopolysaccharide and interferon-gamma requires nuclear factor-kappa B and signal transducer and activator of transcription (STAT) 1.
Murine caspase-11, together with caspase-1, is essential for the production of IL-1beta in response to lipopolysaccharide (LPS). In most cells, caspase-11 is only expressed upon induction with pro-inflammatory stimuli. To understand how caspase-11 expression is transcriptionally regulated, we isolated the caspase-11 gene promoter by genome walking and investigated the mechanisms regulating caspase-11 gene expression in macrophages that are treated with LPS and interferon-gamma. Transient transfections with caspase-11 promoter-luciferase reporter constructs and deletion/mutation analysis revealed an essential role for NF-kappaB binding in the up-regulation of caspase-11 in response to LPS. In the case of interferon-gamma stimulation, signal transducer and activator of transcription 1 binding to the caspase-11 promoter could be shown to be required for caspase-11 expression.
Department of Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, Flanders Interuniversity Institute for Biotechnology, Ghent University, Belgium.
Reinout
R
Schauvliege
Jill
J
Vanrobaeys
Peter
P
Schotte
Rudi
R
Beyaert
D024506:5' Flanking Region; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D020169:Caspases / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*
D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D007371:Interferon-gamma; D004247:DNA; D020169:Caspases