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

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.

Fargesin exerts anti-inflammatory effects in THP-1 monocytes by suppressing PKC-dependent AP-1 and NF-ĸB signaling

“…The pGL3-luciferase reporter plasmid containing IL-1 β, TNF-α, or CCL-5 promoter was constructed as previously described Kim et al, 2015;Kim et al, 2014 ). Cells were seeded in 6-well plates at a density of 10 6 cells/ml and then transiently co-transfected with the IL-1 β, TNF-α or CCL-5 promoter (1 μg/ml) and pRL-null Renilla luciferase plasmid (0.1 μg/ml) using Lipofectamine 20 0 0 (Invitrogen, CA, USA).…”

Interleukin 32: a novel player in the control of infectious diseases

“…In patients with acute myeloid leukemia, the expression of IL-32u is associated with inhibition of TNF-a production. To determine the molecular mechanisms, the authors used THP-1 cells and show that IL-32u inhibits PKC-d activity and, consequently, the p38 phosphorylation and NF-kB activity that decreases TNF-a production [44]. IL-32u also suppresses the production of CCL5 through interaction with PKC-d and inhibition of STAT3 transcriptional activity [45].…”

IL-32: A Novel Pluripotent Inflammatory Interleukin, towards Gastric Inflammation, Gastric Cancer, and Chronic Rhino Sinusitis

“…IL-32 θ expressing group showed a decrease in TNF- α production compared to group without IL-32 θ . It was also reported that, in an IL-32 θ stable expression system, IL-32 θ attenuated the PMA-induced TNF- α production in leukemia cell lines [ 29 ]. Bak et al (2016) reported an inhibition of invasion and migration of colon cancer cells both in vitro and in vivo by ectopic expression of IL-32 θ .…”