Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme.
The interleukin-1beta (IL-1beta) converting enzyme (ICE) processes the inactive IL-1beta precursor to the proinflammatory cytokine. ICE was also shown to cleave the precursor of interferon-gamma inducing factor (IGIF) at the authentic processing site with high efficiency, thereby activating IGIF and facilitating its export. Lipopolysaccharide-activated ICE-deficient (ICE-/-) Kupffer cells synthesized the IGIF precursor but failed to process it into the active form. Interferon-gamma and IGIF were diminished in the sera of ICE-/- mice exposed to Propionibacterium acnes and lipopolysaccharide. The lack of multiple proinflammatory cytokines in ICE-/- mice may account for their protection from septic shock.
Gu
Y
Y
Vertex Pharmaceuticals, Inc., 130 Waverly Street, Cambridge, MA 02139, USA.
Kuida
K
K
Tsutsui
H
H
Ku
G
G
Hsiao
K
K
Fleming
M A
MA
Hayashi
N
N
Higashino
K
K
Okamura
H
H
Nakanishi
K
K
Kurimoto
M
M
Tanimoto
T
T
Flavell
R A
RA
Sato
V
V
Harding
M W
MW
Livingston
D J
DJ
Su
M S
MS
D000818:Animals; D019556:COS Cells; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D053471:Caspases, Initiator; D017077:Culture Media, Conditioned; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D020382:Interleukin-18; D007728:Kupffer Cells / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D014162:Transfection
D017077:Culture Media, Conditioned; D016207:Cytokines; D020382:Interleukin-18; D008070:Lipopolysaccharides; D011498:Protein Precursors; D011994:Recombinant Proteins; D007371:Interferon-gamma; C505407:CASP3 protein, human; C093516:CASP4 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D053471:Caspases, Initiator; D003546:Cysteine Endopeptidases; D020170:Caspase 1