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IL-18 enhances ULBP2 expression through the MAPK pathway in leukemia cells
Hyunkeun Song1, Kyung-Eun Kim, Daeyoung Hur
1Department of Anatomy, Inje University College of Medicine, Pusan 614-735, Republic of Korea.
Immunology Letters
|August 19, 2008
Summary
Interleukin-18 (IL-18) boosts ULBP2 expression in leukemia cells, enhancing Natural Killer (NK) cell cytotoxicity. This occurs through the ERK1/2 and JNK MAPK pathways, suggesting IL-18
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- UL16-binding proteins (ULBPs) are NKG2D ligands expressed in various cancers.
- Factors modulating ULBP expression, particularly in leukemia, are not fully understood.
Purpose of the Study:
- To investigate the effect of Interleukin-18 (IL-18) on NKG2D ligand expression in leukemia cells.
- To elucidate the signaling pathways involved in IL-18-mediated ULBP2 regulation.
Main Methods:
- Leukemia cells were treated with IL-18.
- ULBP2 expression was assessed at mRNA and protein levels.
- MAPK pathway activation (ERK1/2, JNK) and phosphorylation were analyzed.
- Inhibitors of ERK1/2 (PD98059) and JNK (SP600125) were used.
- NK cell cytotoxic activity and CD107a expression were measured.
Main Results:
- IL-18 significantly increased ULBP2 expression in leukemia cells (mRNA and protein).
- IL-18 induced phosphorylation of ERK1/2 and JNK MAPKs.
- MAPK pathway inhibitors dose-dependently attenuated IL-18-induced ULBP2 expression.
- IL-18 enhanced NK cell cytotoxic activity and CD107a expression.
Conclusions:
- IL-18 upregulates ULBP2 expression in leukemia cells via the ERK1/2 and JNK MAPK pathways.
- IL-18 enhances NK cell-mediated cytotoxicity, potentially by increasing target cell susceptibility through ULBP2 induction.
- IL-18 plays a critical role in regulating ULBP2 expression and NK cell immunity in leukemia.
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