Abstract
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 Ets1 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 susceptibility of CML cells. Enhanced NK cell susceptibility of CML cells by IL-32α overexpression may improve the efficiency of NK cell-based immunotherapy.
Highlights
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
We investigated whether overexpression of IL-32 affects susceptibility of chronic myeloid leukemia (CML) cells to NK cells
IL-32␣ Stimulates NK Susceptibility of CML Cells—It has been reported that marrow stromal cells from CML patients have low expression of IL-32, and NK cell activity in CML
Summary
The transcription factor Ets plays a key role in ULBP2 specific expression by IL-32␣ overexpression in ULBP family members Taken together, these data show that IL-32␣ stimulates Fas and ULBP2 expression via activation of p38 MAPK, which increases NK susceptibility of CML cells. We determined that IL-32␣ stimulates Fas and ULBP2 expression on the surface of cells through p38 MAPK activation, and increased Fas and ULBP2 affect enhancement of NK susceptibility of CML cells. These results suggest that IL-32␣ has anticancer characteristics in CML cells
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