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Original Article

Korean J Physiol Pharmacol 2023; 27(5): 471-479

Published online September 1, 2023 https://doi.org/10.4196/kjpp.2023.27.5.471

Copyright © Korean J Physiol Pharmacol.

Dendritic cells resist to disulfiram-induced cytotoxicity, but reduced interleukin-12/23(p40) production

Haebeen Jung1 and Hong-Gu Joo1,2,*

1College of Veterinary Medicine, 2Veterinary Medical Research Institute, Jeju National University, Jeju 63243, Korea

Correspondence to:Hong-Gu Joo
E-mail: jooh@jejunu.ac.kr

Author contributions: H.J. performed the most of experiments. H.G.J. supervised and coordinated the study. H.J. and H.G.J. wrote the manuscript.

Received: May 24, 2023; Revised: June 23, 2023; Accepted: June 27, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Disulfiram (DSF), a medication for alcoholism, has recently been used as a repurposing drug owing to its anticancer effects. Despite the crucial role of dendritic cells (DCs) in immune homeostasis and cancer therapy, the effects of DSF on the survival and function of DCs have not yet been studied. Therefore, we treated bone marrow-derived DCs with DSF and lipopolysaccharide (LPS) and performed various analyses. DCs are resistant to DSF and less cytotoxic than bone marrow cells and spleen cells. The viability and metabolic activity of DCs hardly decreased after treatment with DSF in the absence or presence of LPS. DSF did not alter the expression of surface markers (MHC II, CD86, CD40, and CD54), antigen uptake capability, or the antigen-presenting ability of LPS-treated DCs. DSF decreased the production of interleukin (IL)-12/23 (p40), but not IL-6 or tumor necrosis factor-α, in LPS-treated DCs. We considered the granulocyte-macrophage colony-stimulating factor (GM-CSF) as a factor to make DCs resistant to DSF-induced cytotoxicity. The resistance of DCs to DSF decreased when GM-CSF was not given or its signaling was inhibited. Also, GM-CSF upregulated the expression of a transcription factor XBP-1 which is essential for DCs’ survival. This study demonstrated for the first time that DSF did not alter the function of DCs, had low cytotoxicity, and induced differential cytokine production.

Keywords: Cytotoxicity, Dendritic cells, Disulfiram, Interleukin-12/23(p40), Repurposing drug