Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock.
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.
Li
P
P
BASF Bioresearch Corporation, Worcester, Massachusetts 01605-4314.
Allen
H
H
Banerjee
S
S
Franklin
S
S
Herzog
L
L
Johnston
C
C
McDowell
J
J
Paskind
M
M
Rodman
L
L
Salfeld
J
J
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D020170:Caspase 1; D002678:Chimera; D003546:Cysteine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D017384:Sequence Deletion / Q000502:physiology; D012772:Shock, Septic / Q000139:chemically induced / Q000201:enzymology*; D013950:Thymus Gland / Q000166:cytology
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D003546:Cysteine Endopeptidases; D020170:Caspase 1