Altered Cytokine Export and Apoptosis in Mice Deficient in Interleukin-1β Converting Enzyme

Kuida, Keisuke; Lippke, Judith A.; Ku, George; Harding, Matthew W.; Livingston, David J.; Su, Michael; Flavell, Richard A.

doi:10.1126/science.7535475

Cited by 1,603 publications

(1,168 citation statements)

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“…Also, the caspase inhibitor Z-YVAD-fmk, a potent inhibitor of caspase-1 (Schumann et al, 1998), inhibited khat-induced cell death (Figure 7). IL-1b is a known substrate for caspase-1 (Kuida et al, 1995). However, the role of caspase-1 in induction of apoptosis is controversial (Nicholson and Thornberry, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…However, the role of caspase-1 in induction of apoptosis is controversial (Nicholson and Thornberry, 1997). Overexpression of caspase-1 has induced apoptosis in mammalian cells (Miura et al, 1993), whereas mice deficient in IL-1b develop normally, suggesting a less important role of caspase-1 in regulation of cell death during normal embryogenesis (Kuida et al, 1995). On the other hand, thymocytes from IL-1b-deficient mice were found to be resistant to Fas-induced cell death, showing an impairment of the normal regulation of apoptosis in these cells (Kuida et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

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Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells

et al. 2004

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Khat chewing is a widespread habit that has a deep-rooted sociocultural tradition in Africa and the Middle East. The biological effects of khat are inadequately investigated and controversial. For the first time, we show that an organic extract of khat induces a selective type of cell death having all morphological and biochemical features of apoptotic cell death. Khat extract was shown to contain the major alkaloid compounds cathinone and cathine. The compounds alone and in combination also induced apoptosis. Khat-induced apoptosis occurred synchronously in various human cell lines (HL-60, NB4, Jurkat) within 8 h of exposure. It was partially reversed after removal of khat and the effect was dependent on de novo protein synthesis, as demonstrated by cotreatment with cycloheximide. The cell death was blocked by the pan-caspase inhibitor Z-VAD-fmk, and also by submicromolar concentrations of Z-YVAD-fmk and Z-IETD-fmk, inhibitors of caspase-1 and -8, respectively. The 50% inhibition constant (IC 50 ) for khat (200 mg ml À1 )-induced apoptosis by Z-VAD-fmk, Z-YVAD-fmk and Z-IETD-fmk was 8 Â 10 À7 M as compared to 2 Â 10 À8 M and 8 Â 10 À8 M, respectively. Western blot analysis showed a specific cleavage of procaspase-3 in apoptotic cells, which was inhibited by Z-VAD-fmk. The cell death by khat was more sensitively induced in leukaemia cell lines than in human peripheral blood leukocytes. It is concluded that khat induces a rather swift and sensitive cell death by apoptosis through mechanisms involving activation of caspase-1, -3 and -8.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells

et al. 2004

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“…It has been reported that Fas-and tumor necrosis factor (TNF) receptor-mediated apoptosis is driven by caspase family, because it is suppressed by their inhibitors, including cowpox virus CrmA Enari et al, 1995;Los et al, 1995), baculovirus p35 and tetrapeptide caspase-1 and caspase-3 inhibitors (Enari et al, 1995;Los et al, 1995;Schlegel et al, 1996;Chinnaiyan et al, 1996;Hasegawa et al, 1996). It has also been reported that thymocytes from caspase-1-de®cient mice are resistant to Fas-mediated apoptosis, indicating the direct involvement of caspase-1 itself in this process of thymocyte death (Kuida et al, 1995). Sequential activation of caspase-1(-like) and caspase-3(-like) proteases has been shown to occur in Fas-mediated apoptosis of mouse lymphoma cell line (Enari et al, 1996).…”

Section: Introductionmentioning

confidence: 94%

Involvement of caspase-4(-like) protease in Fas-mediated apoptotic pathway

et al. 1997

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Proteases of the caspase family, especially caspase-1 (ICE)(-like), caspase-3 (CPP32/Yama/apopain)(-like) and caspase-8 (MACH/FLICE/Mch5) proteases, are implicated in Fas (APO-1/CD95)-mediated apoptosis. Here, we show that the caspase-4 (TX/ICH-2/ICE rel II)(-like) protease, another member of the caspase family, is also involved in Fas-mediated apoptosis, based upon the observations: (i) caspase-4 is processed in response to an agonistic anti-Fas antibody treatment, (ii) overexpression of a mutant caspase-4 with active site mutations in both p20 and p10 subunits delays Fas-mediated apoptosis, (iii) microinjected anti-caspase-4 antibodies inhibit Fasmediated apoptosis. Together with our observations that the mutant caspase-4 inhibits the Fas-mediated activation of caspase-3(-like) proteases and puri®ed caspase-4 cleaves pro-caspase-3 to generate a subunit of active form, these results suggest that Fas-mediated apoptosis is driven by a caspase cascade in which the caspase-4(-like) protease transmits a death signal from caspase-8 to caspase-3(-like) proteases probably through directly cleaving pro-caspase-3(-like) proteases.

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“…[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

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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...

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Altered Cytokine Export and Apoptosis in Mice Deficient in Interleukin-1β Converting Enzyme

Cited by 1,603 publications

References 43 publications

Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells

Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells

Involvement of caspase-4(-like) protease in Fas-mediated apoptotic pathway

Inflammatory caspases and inflammasomes: master switches of inflammation

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