Expression Analysis of the Human Caspase-1 Subfamily Reveals Specific Regulation of the CASP5 Gene by Lipopolysaccharide and Interferon-γ

Xiao, Lin; Choi, Michael S.K.; Porter, Alan G.

doi:10.1074/jbc.m007255200

Cited by 170 publications

(151 citation statements)

References 21 publications

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“…We therefore examined whether intermediate doses of LPS that also stimulated sustained IL-18 levels also induced cas-1 mRNA. In agreement with the observations of Lin et al (40), splenic cas-1 mRNA levels were unaffected in mice treated with protective dose LPS compared with those treated with normal saline (vehicle). However, our observation of increased splenic cas-1 mRNA levels in mice treated with intermediate and lethal doses of LPS suggests cas-1 induction as a possible mechanism contributing to the sustained serum IL-18 levels (Fig.…”

Section: Potential Role Of Cas-1 and Serum Il-18 Expression In Responsupporting

confidence: 81%

IL-18 Levels and the Outcome of Innate Immune Response to Lipopolysaccharide: Importance of a Positive Feedback Loop with Caspase-1 in IL-18 Expression

Joshi

Kalvakolanu

Hasday

et al. 2002

The Journal of Immunology

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LPS enhanced antibacterial host defenses (ABHD) when given at low (75 μg) doses (16 of 19 mice survived 3× LD50 Escherichia coli vs 3 of 19 LPS-naive mice; p = 0.0001), but induced lethal inflammation at high (500 μg) doses (5 of 5 died). Differences in the cytokine profiles induced by these LPS doses may provide insight into the mechanism(s) of transition from beneficial to lethal LPS responses. The 75 μg LPS induced 5.9 ± 0.9 ng/ml serum IL-18 at 8 h, which decreased to 2.3 ± 0.4 ng/ml by 24 h, whereas 500 μg LPS induced 11.1 ± 1.6 ng/ml serum IL-18 levels at 8 h, which increased until death. Compared with 75 μg, higher but sublethal (150 μg) doses of LPS induced greater serum IL-18 levels and less effectively induced ABHD (3 of 8 survived). Reduction of serum IL-18 with neutralizing Ab improved the ABHD induced by 150 μg, but reduced that produced by 75 μg LPS, suggesting an optimal range of serum IL-18 level was essential for efficient ABHD. Increased expression of caspase-1 mRNA in response to the higher IL-18 levels induced at the 150 and 500 μg, but not at the 75 μg doses of LPS may represent a positive feedback regulatory loop leading to sustained serum IL-18 levels. We conclude that the regulation of serum IL-18 expression is critical to the outcome of innate immune responses to LPS.

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Section: Potential Role Of Cas-1 and Serum Il-18 Expression In Responsupporting

confidence: 81%

IL-18 Levels and the Outcome of Innate Immune Response to Lipopolysaccharide: Importance of a Positive Feedback Loop with Caspase-1 in IL-18 Expression

Joshi

Kalvakolanu

Hasday

et al. 2002

The Journal of Immunology

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“…Based on expression profiles, caspase-5 was proposed to be the human functional orthologue of caspase-11. 35 Caspase-5 together with caspase-1 were found to be components of the NALP1 inflammasome, a complex involved in the activation of caspase-1 33 (see below). These findings reinforced the hypothesis that different inflammatory caspases may cooperate for full activity.…”

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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“…For example, the basal expression level of caspase-11 in healthy mice and resting cells is very low, but treatment with LPS or other pathological stimuli such as ischemia in vivo leads to a dramatic transcriptional upregulation of caspase-11 expression Kang et al, 2000). The putative human caspase-11 homolog, caspase-5, is also transcriptionally upregulated by LPS (Lin et al, 2000a). Caspase-14 is transcriptionally induced during terminal differentiation of keratinocytes (Eckhart et al, 2000).…”

Section: Gene Expressionmentioning

confidence: 99%

“…Mouse genetic knockout studies have clearly shown that caspsae-11 mediates the activation of caspase-1, which in turn processes cytokines IL-1b and IL-18 (Li et al, 1995;Ghayur et al, 1997;Wang et al, 1998). Lipopolysaccharide (LPS) induces caspase-5 expression in human cells and caspase-11 expression in murine cells Lin et al, 2000a). Caspase-5 together with caspase-1 was found to be the components of the NALP1 inflammasome, a complex involved in the activation of caspase-1 (Martinon et al,…”

Section: Piddosome and Caspase-2 Activationmentioning

confidence: 99%