Caspase-11 Gene Expression in Response to Lipopolysaccharide and Interferon-γ Requires Nuclear Factor-κB and Signal Transducer and Activator of Transcription (STAT) 1

Abstract

Murine caspase-11, together with caspase-1, is essential for the production of IL-1␤ 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-␥. Transient transfections with caspase-11 promoterluciferase reporter constructs and deletion/mutation analysis revealed an essential role for NF-B binding in the up-regulation of caspase-11 in response to LPS. In the case of interferon-␥ stimulation, signal transducer and activator of transcription 1 binding to the caspase-11 promoter could be shown to be required for caspase-11 expression.

Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK Complex

“…11 Caspase-11 induction is regulated by NF-kB. 12,13 Since wedelolactone inhibits the transcriptional increase of caspase-11 induced by LPS, we examined the effect of wedelolactone on the LPS-induced NFkB transcriptional activation in BALB/c cells. The cells transfected with NF-kB or p53 luciferase reporter plasmids were treated with wedelolactone for 1 h, stimulated with LPS for 9 h and then measured for NF-kB or p53 transcriptional activity by the luciferase assay.…”

Guanylate binding proteins promote caspase-11–dependent pyroptosis in response to cytoplasmic LPS

“…and IFNγ both induce the expression of caspase-11 (16), strong evidence exists that additional IFN-inducible host factors other than caspase-11 are needed for the execution of the noncanonical inflammasome pathway (10,14,15,17). To identify IFN-and LPSinducible factors required for the execution of pyroptosis via caspase-11, we pursued a candidate approach.…”

Current insights into the regulation of programmed cell death by NF-κB

“…CYLD has recently been shown to also be important for T-cell development and has been implicated to promote deubiquitination of the T-cell-specific tyrosine kinase Lck (Reiley et al, 2006). NF-kB-induced cell death has also been linked to increased expression of the pro-death factors B7-H1 (PCD ligand 1, pdcd1), which induces apoptosis of T lymphocytes (Dong et al, 2002;Yu et al, 2004;Lee et al, 2005), and caspase-11, which can activate the death effector caspase-3 (Kang et al, 2000;Schauvliege et al, 2002). Additionally, NF-kB can function indirectly to activate genes that regulate cell death via upregulation of other transcription factors like p53 or IRF-1, which acts along with NF-kB to stimulate production of the death-promoting inducible nitric oxide synthase after ischemic injury (Wu and Lozano, 1994;reviewed in Denk et al, 2000).…”