Caspase-1 processes IFN-γ-inducing factor and regulates LPS-induced IFN- γ production

Ghayur, Tariq; Banerjee, Subhashis; Hugunin, M.; Butler, Duncan; Herzog, Linda; Carter, A; Quintal, L.; Sekut, Les; Talanian, Robert V.; Paskind, Michael; Wong, Winnie W.; Kamen, Robert; Tracey, Daniel E.; Allen, Hamish

doi:10.1038/386619a0

Cited by 1,101 publications

(777 citation statements)

References 25 publications

Supporting

Mentioning

746

Contrasting

Unclassified

Order By: Relevance

“…Injection of P. acnes into caspase-1-deficient mice, followed by LPS challenge resulted in low levels of circulating IFNcompared with wild-type mice. [8][9][10][11] Injection of IL-18 restored the IFN-production in response to LPS in the caspase-1-deficient mice, 9 further supporting the concept that caspase-1 is involved in the production of active IL-18. Other caspases, particularly those cleaving intracellular proteins associated with apoptosis, were at least 100-fold less active than caspase-1.…”

mentioning

confidence: 81%

See 1 more Smart Citation

Production of a Biologically Active Human Interleukin 18 Requires Its Prior Synthesis as Pro-Il-18

et al. 2000

View full text Add to dashboard Cite

mentioning

confidence: 81%

“…The resulting mature cytokines are subsequently released from the cell. 8,9 Studies in caspase-1-deficient mice demonstrated the important role of mature IL-18 as an inducer of IFN-and Th 1 responses. Injection of P. acnes into caspase-1-deficient mice, followed by LPS challenge resulted in low levels of circulating IFNcompared with wild-type mice.…”

mentioning

confidence: 99%

Production of a Biologically Active Human Interleukin 18 Requires Its Prior Synthesis as Pro-Il-18

et al. 2000

View full text Add to dashboard Cite

“…[12][13][14][15] These mice have a defect in the maturation of proIL-1b and proIL-18 and are resistant to the lethal effect of endotoxins. IL-18 was first described as an endotoxininduced factor that stimulates the production of interferon-g by splenocytes.…”

Section: Caspase-1 and It Substrate Il-1bmentioning

confidence: 99%

Inflammatory caspases and inflammasomes: master switches of inflammation

2006

View full text Add to dashboard Cite

Fifteen years have passed since the cloning and characterization of the interleukin-1b-converting enzyme (ICE/caspase-1), the first identified member of a family of proteases currently known as caspases. Caspase-1 is the prototypical member of a subclass of caspases involved in cytokine maturation termed inflammatory caspases that also include caspase-4 caspase -5, caspase -11 and caspase -12. Efforts to elucidate the molecular mechanisms involved in the activation of these proteases have uncovered an important role for the NLR family members, NALPs, NAIP and IPAF. These proteins promote the assembly of multiprotein complexes termed inflammasomes, which are required for activation of inflammatory caspases. This article will review some evolutionary aspects, biochemical evidences and genetic studies, underlining the role of inflammasomes and inflammatory caspases in innate immunity against pathogens, autoinflammatory syndromes and in the biology of reproduction. Inflammatory CaspasesThe history of caspases began with the identification of an aspartate-specific protease activity involved in the conversion of the 31 kDa proIL-1b precursor to its active 17 kDa biologically active form, 1,2 and the identification of caspase-1 as the protease responsible for proIL-1b maturation. 3,4 The subsequent discovery of ced-3, that shares similarities with caspase-1 and which is involved in programmed cell death (PCD) in Caenorhabditis elegans, suggested that caspases might play fundamental roles in apoptosis. 5 As reviewed in the papers accompanying this issue of Cell Death and Differentiation, the role of apoptotic caspases in C. elegans and in vertebrates is crucial and deal with many facets of cell biology, development and diseases. In this review, we will focus on a subset of caspases present only in vertebrates and known as inflammatory caspases.Inflammatory caspases (also known as group I caspases) are encoded by three main genes in humans caspase-1, caspase-4 and caspase-5 and three main genes in mouse, caspase-1, caspase-11 and caspase-12. 6,7 In mammals, these caspases are characterized by the presence of a CARD domain at the N-terminus (Figure 1a). Human, chimp and mouse inflammatory caspases share significant similarity and are organized in a single locus (Figure 1c). Phylogenetic analysis of the conserved CARD domain suggests that the inflammatory caspases can be separated in evolutionaryrelated clusters (Figure 1b). The caspase-1 cluster contains caspase-1 and four other genes encoding decoy caspases: cop, inca1, inca2 and iceberg. These decoy caspase-1-like genes are absent in the mouse genome, suggesting that they have arisen recently by duplication of caspase-1. Although human and mouse caspase-1 are likely orthologues, sequence analysis suggests that human caspase-4 and caspase-5 have originated from a duplication of caspase-11. 7 However, the human caspase-12 gene, which in the chimp genome contains an SHG box important for it enzymatic activity, 8 evolved towards an enzymatically inactive form at some stage...

show abstract

“…3 Decreased IFNg production is the hallmark of mice deficient in either IL-18, IL-18 receptor or caspase-1. 4 Several studies have shown elevated circulating IL-18 concentrations in subjects with obesity and insulin resistance, [5][6][7][8][9] and a recent study has demonstrated that a common IL-18 haplotype is associated with a higher body mass index in patients with type 2 diabetes or coronary heart disease. 10 In addition, weight loss after bariatric surgery results in the diminishing of IL-18 concentrations in the blood.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus

et al. 2008

View full text Add to dashboard Cite

Objective: Interleukin-18 (IL-18) has been recently demonstrated to improve experimental hyperphagia and insulin resistance. Paradoxically, concentrations of circulating IL-18 in obese subjects and in patients with type 2 diabetes are increased. The objective of this study is to provide an explanation for this paradox. Design: We have hypothesized that cells from obese individuals or from patients with type 2 diabetes mellitus have a diminished response to stimulation with IL-18. IL-18 responsiveness was tested by stimulating blood monocytes of obese or diabetes patients with rIL-18 or microbial components. Results: Obese individuals and patients with type 2 diabetes mellitus exhibit increased circulating concentrations of IL-18. More importantly, leukocytes isolated from obese or type 2 diabetes patients respond poorly after stimulation with IL-18, as reflected by defective interferon-g (IFNg) production. The defective response to IL-18 stimulation was accompanied by a 50% reduction in the expression of IL-18R a and b chains. In addition, cells of patients with obesity and diabetes displayed an impaired release of IFNg after challenge with bacterial or fungal pathogens, which was due to defective IL-18-mediated signaling. Conclusion: Patients with obesity or type 2 diabetes mellitus are characterized by lower responses after stimulation with IL-18. This IL-18 resistance explains the association of obesity and diabetes with high IL-18 circulating concentrations, similar to hyperinsulinemia and hyperleptinemia. IL-18 resistance may represent an important mechanism of the increased susceptibility of these patients to a number of infections.

show abstract

Caspase-1 processes IFN-γ-inducing factor and regulates LPS-induced IFN- γ production

Cited by 1,101 publications

References 25 publications

Production of a Biologically Active Human Interleukin 18 Requires Its Prior Synthesis as Pro-Il-18

Production of a Biologically Active Human Interleukin 18 Requires Its Prior Synthesis as Pro-Il-18

Inflammatory caspases and inflammasomes: master switches of inflammation

Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus

Contact Info

Product

Resources

About