Work

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

Year: 2015

Type: article

Abstract: // Man Sub Kim 1 , Jeong-Woo Kang 1, 5 , Jae-Sik Jeon 2 , Jae Kyung Kim 3 , Jong Wan Kim 2 , Jintae Hong 4 , Do-Young Yoon 1 1 Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea 2 Department of Laboratory Medicine, Dankook University College of Medicine, Cheonan, Korea 3 Dankook University College of Health Sciences, Department of Biomedical Laboratory Science, Cheonan, Korea 4 College of Pharmacy, Medical Research Center, Chungbuk National University, Chungbuk, Korea 5 Current address: Seegene Inc., Seoul, Korea Correspondence to: Do-Young Yoon, e-mail: [email protected] 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.

Source: Oncotarget

DOI: 10.18632/oncotarget.5688