4-hydroxynonenal inhibits interleukin-1β converting enzyme

Darren W. Davis, Raymond F. Hamilton, Andrij Holian

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Lipid peroxidation results from the interaction of reactive oxygen species and polyunsaturated fatty acids. Metabolites generated from oxidative stress play an important role in the pathogenesis of a variety of diseases and biologic processes. One such product generated from lipid peroxidation is 4-hydroxynonenal (HNE). HNE is thiol reactive and exhibits numerous cellular effects. In this study, the inhibition of the cysteine protease, interleukin- 1β (IL-1β) converting enzyme (ICE), by HNE in human blood mononuclear cells was investigated. HNE blocked the release of lipopolysaccharide (LPS)- stimulated IL-1β (EC50 5 μM) and IL-10 (EC50 2 μM) in a dose-dependent manner and, to a lesser extent, tumor necrosis factor-α (TNF-α) (EC50 15 μM) release. However, LPS-stimulated elevation of intracellular proIL-1β levels was not affected by HNE treatment. HNE inhibited ICE activity in lysed cells in a similar dose-dependent manner, measured by hydrolysis of the fluorogenic substrate YVAD-AMC and recombinant proIL-1β. To confirm that the inhibition of ICE activity by HNE was not an indirect effect, ICE activity was examined using purified recombinant human ICE (rHu-ICE). HNE inhibited rHu-ICE activity in a dose-dependent manner. Thus, low levels of HNE can suppress mononuclear cell release of IL-1β, probably by interacting with the active site cysteine of ICE. These results have implications for modulating mononuclear cell function during oxidative stress conditions.

Original languageEnglish
Pages (from-to)205-210
Number of pages6
JournalJournal of Interferon and Cytokine Research
Issue number4
StatePublished - Apr 1997


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