IL-18 enhances ULBP2 expression through the MAPK pathway in leukemia cells.
Expression of UL16-binding proteins (ULBPs) has been reported in various cancers, such as leukemia and melanoma, and also in some other cancer cell lines. However, the factors that modulate the expression of ULBPs are not well defined. In this study, we investigated the effects of IL-18 on the expression of NKG2D ligands in leukemia cells. IL-18 treatment increased ULBP2 expression in leukemia cells at the mRNA and protein levels. In addition, PD98059 (an ERK1/2 MAPK inhibitor) and SP600125 (a JNK inhibitor) attenuated IL-18-induced ULBP2 expression in a dose-dependent manner. We observed that ERK1/2 and JNK MAPK phosphorylation increased upon treatment with IL-18. IL-18 elevated CD107a expression in cancer cells and increased the cytotoxic activity of NK cells; therefore, we propose that IL-18 increases the susceptibility of target cells by inducing surface expression of ULBP2. Taken together, these findings suggest that IL-18 may play a critical role in regulating ULBP2 expression via the ERK1/2 and JNK MAPK pathways in leukemia cells.
Song
Hyunkeun
H
Department of Anatomy, Inje University College of Medicine, Pusan 614-735, Republic of Korea.
Kim
Kyung-Eun
KE
Hur
Daeyoung
D
Lim
Jong-Seok
JS
Yang
Young
Y
Cho
Byung Joo
BJ
Kim
Cherl-Hyun
CH
Kim
Taesung
T
Bang
Saic
S
Lee
Wang Jae
WJ
Park
Hyunjeong
H
Cho
Daeho
D
D000873:Anthracenes / Q000494:pharmacology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D020382:Interleukin-18 / Q000494:pharmacology*; D019169:Jurkat Cells; D007938:Leukemia / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*
D000873:Anthracenes; D005419:Flavonoids; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; C423230:ULBP2 protein, human; C432165:pyrazolanthrone; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one