Distinct downstream pathways of caspase-11 in regulating apoptosis and cytokine maturation during septic shock response

Cell Death Differ. 2002 Oct;9(10):1115-25. doi: 10.1038/sj.cdd.4401087.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / immunology*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology
  • BH3 Interacting Domain Death Agonist Protein
  • Carrier Proteins / drug effects
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism
  • Caspase 1 / drug effects
  • Caspase 1 / immunology
  • Caspase 1 / metabolism
  • Caspase 3
  • Caspases / deficiency*
  • Caspases / drug effects
  • Caspases / genetics
  • Caspases / immunology
  • Caspases / metabolism
  • Caspases, Initiator
  • Cytokines / biosynthesis*
  • Cytokines / immunology
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Female
  • Immunohistochemistry
  • Inflammation / enzymology*
  • Inflammation / immunology
  • Inflammation / prevention & control
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Knockout
  • Shock, Septic / drug therapy
  • Shock, Septic / enzymology*
  • Shock, Septic / immunology
  • Spleen / drug effects
  • Spleen / enzymology
  • Spleen / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology

Substances

  • BH3 Interacting Domain Death Agonist Protein
  • Bid protein, mouse
  • Carrier Proteins
  • Cytokines
  • Lipopolysaccharides
  • CASP3 protein, human
  • Casp3 protein, mouse
  • Casp4 protein, mouse
  • Caspase 3
  • Caspases
  • Caspases, Initiator
  • Caspase 1