Mice Deficient in IL-1 Beta-Converting Enzyme Are Defective in Production of Mature IL-1 Beta and Resistant to Endotoxic Shock

Cell. 1995 Feb 10;80(3):401-11. doi: 10.1016/0092-8674(95)90490-5.

Abstract

IL-1 beta-converting enzyme (ICE) cleaves pro-IL-1 beta to generate mature IL-1 beta. ICE is homologous to other proteins that have been implicated in apoptosis, including CED-3 and Nedd-2/lch-1. We generated ICE-deficient mice and observed that they are overtly normal but have a major defect in the production of mature IL-1 beta after stimulation with lipopolysaccharide. IL-1 alpha production is also impaired. ICE-deficient mice are resistant to endotoxic shock. Thymocytes and macrophages from the ICE-deficient animals undergo apoptosis normally. ICE therefore plays a dominant role in the generation of mature IL-1 beta, a previously unsuspected role in production of IL-1 alpha, but has no autonomous function in apoptosis.

MeSH terms

  • Animals
  • Apoptosis
  • Base Sequence
  • Caspase 1
  • Chimera
  • Cysteine Endopeptidases / deficiency
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • Cytokines / blood
  • Female
  • Interleukin-1 / biosynthesis*
  • Interleukin-1 / blood
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation / drug effects
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • RNA, Messenger / biosynthesis
  • Sequence Deletion / physiology
  • Shock, Septic / chemically induced
  • Shock, Septic / enzymology*
  • Thymus Gland / cytology

Substances

  • Cytokines
  • Interleukin-1
  • Lipopolysaccharides
  • RNA, Messenger
  • Cysteine Endopeptidases
  • Caspase 1