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In vitro and in vivo studies of ICE inhibitors
Author(s) -
Livingston David J.
Publication year - 1997
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(199701)64:1<19::aid-jcb4>3.0.co;2-2
Subject(s) - in vivo , in vitro , chemistry , computational biology , microbiology and biotechnology , biology , biochemistry
Interleukin‐1β‐converting enzyme (ICE) is a cysteine protease responsible for proteolytic activation of the biologically inactive interleukin‐1β 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‐1β 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. J. Cell. Biochem. 64:19–26. © Wiley‐Liss, Inc.