title: Overexpression of IL-32alpha increases natural killer cell-mediated killing through up-regulation of Fas and UL16-binding protein 2 (ULBP2) expression in human chronic myeloid leukemia cells.
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.
authors.affiliation: Department of Life Science, Sookmyung Women's University, and Konkuk University Hospital, Seoul 140-742, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Cheon
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Lee
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Park
authors.forename: Sa Ik
authors.initials: SI
authors.lastname: Bang
authors.forename: Wang Jae
authors.initials: WJ
authors.lastname: Lee
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon
authors.forename: Taesung
authors.initials: T
authors.lastname: Kim
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Min
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Cho
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Ki Woong
authors.initials: KW
authors.lastname: Lee
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Jeong
authors.forename: Hyunjeong
authors.initials: H
authors.lastname: Park
authors.forename: Daeho
authors.initials: D
authors.lastname: Cho
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C494041:ETS1 protein, human; C491901:FAS protein, human; D058851:GPI-Linked Proteins; C496971:IL32 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D007378:Interleukins; D050784:Proto-Oncogene Protein c-ets-1; D034741:RNA, Small Interfering; C423230:ULBP2 protein, human; D019014:fas Receptor; D048051:p38 Mitogen-Activated Protein Kinases