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The proinflammatory cytokine interleukin-18 alters multiple signaling pathways to inhibit natural killer cell death

Journal of Interferon and Cytokine Research

By:
, , , , , , ,
DOI: 10.1089/jir.2006.26.706

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Abstract

The proinflammatory cytokine, interleukin-18 (IL-18), is a natural killer (NK) cell activator that induces NK cell cytotoxicity and interferon-?? (IFN-??) expression. In this report, we define a novel role for IL-18 as an NK cell protective agent. Specifically, IL-18 prevents NK cell death initiated by different and distinct stress mechanisms. IL-18 reduces NK cell self-destruction during NK-targeted cell killing, and in the presence of staurosporin, a potent apoptotic inducer, IL-18 reduces caspase-3 activity. The critical regulatory step in this process is downstream of the mitochondrion and involves reduced cleavage and activation of caspase-9 and caspase-3. The ability of IL-18 to regulate cell survival is not limited to a caspase death pathway in that IL-18 augments tumor necrosis factor (TNF) signaling, resulting in increased and prolonged mRNA expression of c-apoptosis inhibitor 2 (cIAP2), a prosurvival factor and caspase-3 inhibitor, and TNF receptor-associated factor 1 (TRAF1), a prosurvival protein. The cumulative effects of IL-18 define a novel role for this cytokine as a molecular survival switch that functions to both decrease cell death through inhibition of the mitochondrial apoptotic pathway and enhance TNF induction of prosurvival factors. ?? Mary Ann Liebert, Inc.

Additional Publication Details

Publication type:
Article
Publication Subtype:
Journal Article
Title:
The proinflammatory cytokine interleukin-18 alters multiple signaling pathways to inhibit natural killer cell death
Series title:
Journal of Interferon and Cytokine Research
DOI:
10.1089/jir.2006.26.706
Volume
26
Issue:
10
Year Published:
2006
Language:
English
Larger Work Type:
Article
Larger Work Subtype:
Journal Article
First page:
706
Last page:
718
Number of Pages:
13