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

TLDR

The interleukin‑1β converting enzyme (ICE) activates the proinflammatory cytokine IL‑1β by proteolytic cleavage of its precursor. ICE also efficiently cleaves the interferon‑γ inducing factor precursor, activating IGIF and promoting its secretion; ICE‑deficient Kupffer cells fail to process IGIF, leading to reduced IGIF and IFN‑γ levels and conferring protection against septic shock.

Abstract

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.