Abstract
Fas ligand is a well-characterized apoptosis inducer. Here we demonstrate that Fas ligand induces the processing and secretion of interleukin-1beta (IL-1beta) in peritoneal exudate cells. This IL-1beta secretion is independent of IL-1beta converting enzyme (caspase 1), yet it is inhibited by caspase inhibitors, indicating that a caspase(s) in addition to IL-1beta converting enzyme can process IL-1beta. Inoculation of tumor cells expressing Fas ligand into wild-type mice induces a massive neutrophil infiltration that is, in contrast, suppressed in IL-1alpha/beta knockout mice. These results demonstrate a newly discovered role for Fas ligand in inflammation, and challenge the dogma that apoptosis does not induce inflammation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis*
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Caspase 1 / deficiency
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Caspase 1 / genetics
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Caspase 1 / metabolism*
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Cells, Cultured
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Crosses, Genetic
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Fas Ligand Protein
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Female
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Fibrosarcoma / immunology
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Fibrosarcoma / pathology
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Homozygote
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Inflammation / immunology
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Inflammation / physiopathology*
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Interleukin-1 / biosynthesis*
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Interleukin-1 / deficiency
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Interleukin-1 / genetics
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Lymphocytes / immunology
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Male
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Mice, Knockout
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Neutrophils / physiology
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Reverse Transcriptase Polymerase Chain Reaction
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Spleen / immunology
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fas Receptor / physiology*
Substances
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Fas Ligand Protein
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Fasl protein, mouse
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Interleukin-1
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Membrane Glycoproteins
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fas Receptor
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Caspase 1