In vitro and in vivo studies of ICE inhibitors

✍ Scribed by David J. Livingston

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 81 KB
• Volume: 64
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(199701)64:1<19::aid-jcb4>3.0.co;2-2

✦ Synopsis

Interleukin-1b-converting enzyme (ICE) is a cysteine protease responsible for proteolytic activation of the biologically inactive interleukin-1b precursor to the proinflammatory cytokine. ICE and homologous proteases also appear to mediate intracellular protein degradation during programmed cell death. Inhibition of ICE is a new antiinflammatory strategy being explored by the design of both reversible inhibitors and irreversible inactivators of the enzyme. Such compounds are capable of blocking release of interleukin-1b from human monocytes. ICE inhibitors that cross react against multiple ICE homologs can also block apoptosis in diverse cell types. ICE inhibitors impart protection in vivo from endotoxin-induced sepsis and collagen-induced polyarthritis in rodent models. Further optimization of the current generation of peptidyl ICE inhibitors will be required to produce agents suitable for administration in chronic inflammatory and neurodegenerative diseases.