Overexpression of IL-32α Increases Natural Killer Cell-mediated Killing through Up-regulation of Fas and UL16-binding protein 2 (ULBP2) Expression in Human Chronic Myeloid Leukemia Cells.

IL-32 was recently identified as a proinflammatory cytokine that is induced by IL-18 in natural killer (NK) cells and is highly correlated with inflammatory disorders. However, the relationship between IL-32 and tumor progression is still unknown. In this study, we investigated whether overexpression of IL-32 affects susceptibility of chronic myeloid leukemia (CML) cells to NK cells. Interestingly, IL-32α-overexpressing CML cell lines, K562, Kcl22, and BV173, showed higher NK cell-mediated killing. Flow cytometry analysis revealed that overexpression of IL-32α induced increased expression of Fas and UL16-binding protein 2 (ULBP2) in CML cells. The direct relationship between overexpression of surface molecules by IL-32α and increased NK cell-mediated killing was confirmed by Fas or ULBP2 siRNA transfection. IL-32α-induced Fas and ULBP2 expression are regulated p38 MAPK. In addition, the transcription factor Etsi plays a key role in ULBP2 specific expression by IL-32α overexpression in ULBP family members. Taken together) these data show that IL-32α stimulates Fas and ULBP2 expression via activation of p38 MAPK, which increases NK sus- ceptibility of CML cells. Enhanced NI( cell susceptibility of CML cells by IL-32α overexpression may improve the efficiency ófNK cell-based immunotherapy. [ABSTRACT FROM AUTHOR]