Abstract
Caspase-11 is an essential mediator of septic shock response and caspase-11-deficient mice are resistant to LPS-induced shock. Here we report that LPS-induced caspase-11 regulates lymphocyte apoptosis by activating both caspase-3 and caspase-7. The activation of caspase-11 preceded that of caspase-1 and caspases-3/-7, and in the absence of caspase-11, the activation of caspases-3/-7 was significantly reduced. The early activation of caspases-3/-7 by caspase-11 was not affected by blocking of caspase-1 activity and IL-1beta release, implying that caspase-11 activates caspases-3/-7 independently of caspase-1 activation. Furthermore, we show that caspase-11-mediated apoptosis under septic condition is Bid-independent. Our work suggests that the human homologue of caspase-11 may be an effective therapeutic target for treatment of septic shock.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / immunology*
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B-Lymphocytes / drug effects
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B-Lymphocytes / enzymology
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B-Lymphocytes / immunology
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BH3 Interacting Domain Death Agonist Protein
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Carrier Proteins / drug effects
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Carrier Proteins / immunology
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Carrier Proteins / metabolism
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Caspase 1 / drug effects
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Caspase 1 / immunology
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Caspase 1 / metabolism
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Caspase 3
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Caspases / deficiency*
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Caspases / drug effects
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Caspases / genetics
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Caspases / immunology
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Caspases / metabolism
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Caspases, Initiator
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Cytokines / biosynthesis*
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Cytokines / immunology
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Disease Models, Animal
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Down-Regulation / drug effects
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Down-Regulation / immunology
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Female
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Immunohistochemistry
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Inflammation / enzymology*
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Inflammation / immunology
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Inflammation / prevention & control
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Lipopolysaccharides
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Macrophages / drug effects
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Macrophages / enzymology
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Macrophages / immunology
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Male
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Mice
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Mice, Knockout
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Shock, Septic / drug therapy
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Shock, Septic / enzymology*
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Shock, Septic / immunology
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Spleen / drug effects
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Spleen / enzymology
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Spleen / immunology
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T-Lymphocytes / drug effects
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T-Lymphocytes / enzymology
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T-Lymphocytes / immunology
Substances
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BH3 Interacting Domain Death Agonist Protein
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Bid protein, mouse
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Carrier Proteins
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Cytokines
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Lipopolysaccharides
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CASP3 protein, human
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Casp3 protein, mouse
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Casp4 protein, mouse
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Caspase 3
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Caspases
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Caspases, Initiator
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Caspase 1