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

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Haebeen Jung Hong-Gu Joo
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제27권 제5호, 471~479쪽, 전체 9쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2023.09.30

영문 초록

Disulfiram (DSF), a medication for alcoholism, has recently been used as a repurposing drug owing to its anticancer effects. Despite the crucial role of den-dritic 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 expres-sion 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.

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키워드

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