DOI: 10.1126/science.275.5297.206 ISSN:
Activation of Interferon-γ Inducing Factor Mediated by Interleukin-1β Converting Enzyme
Yong Gu, Keisuke Kuida, Hiroko Tsutsui, George Ku, Kathy Hsiao, Mark A. Fleming, Nobuki Hayashi, Kazuya Higashino, Haruki Okamura, Kenji Nakanishi, Masashi Kurimoto, Tadao Tanimoto, Richard A. Flavell, Vicki Sato, Matthew W. Harding, David J. Livingston, Michael S.-S. Su- Multidisciplinary
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 toPropionibacterium acnesand lipopolysaccharide. The lack of multiple proinflammatory cytokines in ICE−/−mice may account for their protection from septic shock.