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

Soyoung Cheon, Ji Hyung Lee, Sunyoung Park, Sa Ik Bang, Wang Jae Lee, Do Young Yoon, Sung Soo Yoon, Tae Sung Kim, Hyeyoung Min, Byung Joo Cho, Hyong Joo Lee, Ki Woong Lee, Seung Hwan Jeong, Hyunjeong Park, Dae Ho Cho

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)12049-12055
Number of pages7
JournalJournal of Biological Chemistry
Volume286
Issue number14
DOIs
Publication statusPublished - 2011 Apr 8

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Myeloid Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Natural Killer Cells
Carrier Proteins
Up-Regulation
p38 Mitogen-Activated Protein Kinases
Interleukin-18
Flow cytometry
Population Growth
Small Interfering RNA
Tumors
Transcription Factors
Immunotherapy
Chemical activation
Transfection
Cells
Cytokines
Flow Cytometry
Molecules
Cell Line

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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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. / Cheon, Soyoung; Lee, Ji Hyung; Park, Sunyoung; Bang, Sa Ik; Lee, Wang Jae; Yoon, Do Young; Yoon, Sung Soo; Kim, Tae Sung; Min, Hyeyoung; Cho, Byung Joo; Lee, Hyong Joo; Lee, Ki Woong; Jeong, Seung Hwan; Park, Hyunjeong; Cho, Dae Ho.

In: Journal of Biological Chemistry, Vol. 286, No. 14, 08.04.2011, p. 12049-12055.

Research output: Contribution to journalArticle

Cheon, Soyoung ; Lee, Ji Hyung ; Park, Sunyoung ; Bang, Sa Ik ; Lee, Wang Jae ; Yoon, Do Young ; Yoon, Sung Soo ; Kim, Tae Sung ; Min, Hyeyoung ; Cho, Byung Joo ; Lee, Hyong Joo ; Lee, Ki Woong ; Jeong, Seung Hwan ; Park, Hyunjeong ; Cho, Dae Ho. / 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. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 14. pp. 12049-12055.
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AU - Park, Sunyoung

AU - Bang, Sa Ik

AU - Lee, Wang Jae

AU - Yoon, Do Young

AU - Yoon, Sung Soo

AU - Kim, Tae Sung

AU - Min, Hyeyoung

AU - Cho, Byung Joo

AU - Lee, Hyong Joo

AU - Lee, Ki Woong

AU - Jeong, Seung Hwan

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