Activation of Interferon-γ Inducing Factor Mediated by Interleukin-1β Converting Enzyme

• Published in: Science (American Association for the Advancement of Science) Vol. 275; no. 5297; pp. 206 - 209
• Main Authors: Gu, Yong, Kuida, Keisuke, Tsutsui, Hiroko, Ku, George, Hsiao, Kathy, Fleming, Mark A., Hayashi, Nobuki, Higashino, Kazuya, Okamura, Haruki, Nakanishi, Kenji, Kurimoto, Masashi, Tanimoto, Tadao, Flavell, Richard A., Sato, Vicki, Harding, Matthew W., Livingston, David J., Michael S.-S. Su
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 10.01.1997; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Cellular biology; Cellular immunity; COS cells; Cultured cells; Cytokines; Enzymes; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Ice; Immunobiology; Interleukins; Kupffer cells; Medical research; Mice; Miscellaneous; Physiological aspects; Plasmids; Proteases; Regulatory factors and their cellular receptors; Splenocytes; T lymphocytes; Molecular processing; Enzyme; Cysteine endopeptidases; Liver; Rodentia; Immune regulation; Inflammation; Peptidases; Kupffer cell; Vertebrata; Regulation(control); Cell line; Mammalia; Gene; Interleukin 1-β converting enzyme; Mouse; Hydrolases; Mutation; Gamma interferon; Macrophage
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.275.5297.206

The interleukin-1β (IL-1β) converting enzyme (ICE) processes the inactive IL-1β precursor to the proinflammatory cytokine. ICE was also shown to cleave the precursor of interferon-γ 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-γ 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.