Abstract
Interleukin-1 beta converting enzyme (ICE) processes the inactive prolL-1 beta to the proinflammatory mature IL-1 beta. ICE belongs to a family of cysteine proteases that have been implicated in apoptosis. To address the biological functions of ICE, we generated ICE-deficient mice through gene targeting technology. ICE-deficient mice developed normally, appeared healthy, and were fertile. Peritoneal macrophages from ICE-deficient mice underwent apoptosis normally upon ATP treatment. Thymocytes from young ICE-deficient mice also underwent apoptosis when triggered by dexamethasone, gamma irradiation, or aging. ICE-deficient mice had a major defect in the production of mature IL-1 beta and had impaired IL-1 alpha production on LPS stimulation in vitro and in vivo. ICE-deficient mice were resistant to LPS-induced endotoxic shock.
MeSH terms
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Adenosine Triphosphate / pharmacology
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Age Factors
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology*
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Apoptosis / radiation effects
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Caspase 1
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Cysteine Endopeptidases / deficiency*
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Cysteine Endopeptidases / genetics*
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Cysteine Endopeptidases / physiology
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Dexamethasone / pharmacology
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Dose-Response Relationship, Drug
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Female
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Galactosamine / pharmacology
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Gamma Rays
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Heterozygote
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Interleukin-1 / biosynthesis*
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Lipopolysaccharides / toxicity
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Macrophages / drug effects
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Macrophages / metabolism*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Mutation
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Phenotype
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Recombination, Genetic
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Shock, Septic / metabolism
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Thymus Gland / cytology
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Thymus Gland / drug effects
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Thymus Gland / radiation effects
Substances
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Interleukin-1
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Lipopolysaccharides
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Galactosamine
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Dexamethasone
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Adenosine Triphosphate
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Cysteine Endopeptidases
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Caspase 1