The proinflammatory cytokine interleukin-18 alters multiple signaling pathways to inhibit natural killer cell death
Journal of Interferon and Cytokine Research
By: D. L. Hodge, J.J. Subleski, D. A. Reynolds, M.D. Buschman, W. B. Schill, M.W. Burkett, A.M. Malyguine, and H. A. Young
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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.
Suggested Citation
Hodge, D.L., Subleski, J., Reynolds, D.A., Buschman, M., Schill, W.B., Burkett, M., Malyguine, A., Young, H., 2006, The proinflammatory cytokine interleukin-18 alters multiple signaling pathways to inhibit natural killer cell death: Journal of Interferon and Cytokine Research, v. 26, no. 10, p. 706-718, https://doi.org/10.1089/jir.2006.26.706.
| 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 |
| Larger Work Title | Journal of Interferon and Cytokine Research |
| First page | 706 |
| Last page | 718 |