Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE

S Wang1, M Miura, Y K Jung

  • 1Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Cell
|March 10, 1998
PubMed

Insights

Caspase-11 (casp-11) gene inactivation renders mice resistant to endotoxic shock. Caspase-11 is essential for Interleukin-1 converting enzyme (ICE) activation, suggesting it

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Death Research

Background:

  • The Ice/Ced-3 (caspase) gene family plays a critical role in programmed cell death.
  • Interleukin-1 converting enzyme (ICE) activation is a key event in inflammatory responses like septic shock.

Purpose of the Study:

  • To investigate the role of caspase-11 (casp-11) in cell death pathways and inflammatory responses.
  • To determine if casp-11 is involved in the activation of ICE.

Main Methods:

  • Gene targeting to create casp-11 mutant mice.
  • Analysis of endotoxic shock resistance in mutant mice.
  • Assessment of IL-1alpha and IL-1beta production following lipopolysaccharide stimulation.
  • Apoptosis assays using casp-11 mutant embryonic fibroblast cells.
  • Co-immunoprecipitation to study protein interactions between pro-caspase-11 and pro-ICE.

Main Results:

  • Casp-11 mutant mice exhibit resistance to lipopolysaccharide-induced endotoxic shock.
  • Production of IL-1alpha and IL-1beta is blocked in casp-11 mutant mice after lipopolysaccharide stimulation.
  • Casp-11 mutant cells are resistant to apoptosis induced by ICE overexpression.
  • Pro-caspase-11 physically interacts with pro-ICE in cells.
  • Caspase-11 expression is crucial for ICE activation.

Conclusions:

  • Caspase-11 is a necessary component of the ICE complex.
  • Caspase-11 is required for the activation of ICE, playing a vital role in inflammatory signaling and cell death.

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