Oncotarget

Research Papers:

IL-32θ gene expression in acute myeloid leukemia suppresses TNF-α production

Man Sub Kim _, Jeong-Woo Kang, Jae-Sik Jeon, Jae Kyung Kim, Jong Wan Kim, Jintae Hong and Do-Young Yoon

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Oncotarget. 2015; 6:40747-40761. https://doi.org/10.18632/oncotarget.5688

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Abstract

Man Sub Kim1, Jeong-Woo Kang1,5, Jae-Sik Jeon2, Jae Kyung Kim3, Jong Wan Kim2, Jintae Hong4, Do-Young Yoon1

1Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea

2Department of Laboratory Medicine, Dankook University College of Medicine, Cheonan, Korea

3Dankook University College of Health Sciences, Department of Biomedical Laboratory Science, Cheonan, Korea

4College of Pharmacy, Medical Research Center, Chungbuk National University, Chungbuk, Korea

5Current address: Seegene Inc., Seoul, Korea

Correspondence to:

Do-Young Yoon, e-mail: ydy4218@konkuk.ac.kr

Keywords: IL-32, TNF-α, acute myeloid leukemia (AML), NF-κB

Received: January 06, 2015     Accepted: September 15, 2015     Published: October 16, 2015

ABSTRACT

The proinflammatory cytokine TNF-α is highly expressed in patients with acute myeloid leukemia (AML) and has been demonstrated to induce rapid proliferation of leukemic blasts. Thus suppressing the production of TNF-α is important because TNF-α can auto-regulate own expression through activation of NF-κB and p38 mitogen-activated protein kinase (MAPK). In this study, we focused on the inhibitory effect of IL-32θ on TNF-α production in acute myeloid leukemia. Approximately 38% of patients with AML express endogenous IL-32θ, which is not expressed in healthy individuals. Furthermore, plasma samples were classified into groups with or without IL-32θ; then, we measured proinflammatory cytokine TNF-α, IL-1β, and IL-6 levels. TNF-α production was not increased in patients with IL-32θ expression than that in the no-IL-32θ group. Using an IL-32θ stable expression system in leukemia cell lines, we found that IL-32θ attenuated phorbol 12-myristate 13-acetate (PMA)-induced TNF-α production. IL-32θ inhibited phosphorylation of p38 MAPK, inhibitor of κB (IκB), and nuclear factor κB (NF-κB), which are key positive regulators of TNF-α expression, and inhibited nuclear translocation of NF-κB. Moreover, the presence of IL-32θ attenuated TNF-α promoter activity and the binding of NF-κB with the TNF-α promoter. In addition, IL-32γ-induced TNF-α production has no correlation with inhibition of TNF-α via IL-32θ expression. Thus, IL-32θ may serve as a potent inhibitor of TNF-α in patients with AML.


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