• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.79-86
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• 2001

Recent clinical studies have shown that a high proportion of patients with acute promyelocytic leukemia (APL) achieve complete remission after treatment with all-trans retinoic acid (ATRA). However, most patients who receive continuous treatment with ATRA relapse and develop ATRA-resistant leukemia. Dendritic cells (DCs) are important antigen-presenting cells in the development of antileukemic T-cell responses. In this study, we investigated the strategies to overcome ATRA resistance of APL cells by inducing the differentiation of DCs from human leukemic cell lines for the developtment of adoptive immunotherapy. CD83 was used as a mature DC marker in this study and the expression of CD83 mRNA was determined by RT-PCR method. The promyelocytic leukemic cell line HL-60, B lymphoblast cell lines RPMI 7666 and NC-37 could be induced to dendritic cells in vitro. Treatment of HL-60 with phorbol 12-myristate 13-acetate (PMA) resulted in the expression of myeloid-related DC phenotypes, while treatment of RPMI 7666 with fms-like tyrosine kinase 3 ligand (Flt3-ligand, FL) and treatment of NC-37 with PMA and FL led to the expression of lymphoid-related DC phenotypes. In conclusion, myeloid-related DC phenotypes and lymphoid-related DC phenotypes could be generated from HL-60, NC-37 and RPMI 7666 cell lines, respectively. These DC phenotypes can potentially be used to generate antileukemic T cells in vitro for adoptive immunotherapy.

• BMB Reports
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• v.43 no.3
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• pp.188-192
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• 2010

Inflammatory reactology has become increasingly important in diabetic kidney disease. In this study, we estabilished STZ-induced diabetic rat model to investigate whether dendritic cells (DCs) mediated tubulointerstitial damages, and whether the effects by DCs were mediated by P-selectin expression and can be inhibited by atorvastatin. The study demonstrated that there was an accumulation of DCs in diabetic rats mediated by P-selectin. It also showed the accumulation of DCs and expression of P-selectin was closely correlated with the degree of renal tubulointerstitial injury. These effects were markedly attenuated by atorvastatin. Thus, DCs play a role in tubulointerstitial damages, atorvasttin can prevent renal tubulointerstitium from damage by inhibiting the P-selectin expression and DCs migration.

• Proceedings of the Korean Vacuum Society Conference
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• 2014.02a
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• pp.132.1-132.1
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• 2014

Fluorescent-magnetic nanoclusters were synthesized for biomedical applications. The nanoclusters consisted of superparamagnetic core-nanoclusters, highly fluorescent shell of nanocrystals, and lipid A. Magnetic cores were used for both magnetic resonance imaging (MRI) and cell separation. Fluorescent shell was used for optical imaging. The lipid-A-loaded nanoclusters were up-taken by dendritic cells via phagocytosis, which successfully activated dendritic cells. The dendritic cells were migrated to lymph nodes and spleen of mice. The results showed that our novel nanoclusters can play a role as an efficient optical and magnetic imaging, a cell separating and a pathogen mimetic agent at the same time. Additionally, synthesis of wavelength conversion nanowires will be discussed, which may be used as an optical nanoprobe in biological studies.

• Korean Journal of Microbiology
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• v.54 no.3
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• pp.222-227
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• 2018

Mycobacterium tuberculosis (MTB)-originated lipid antigen is presented on the antigen-presenting cell surface with CD1b. When monocyte-derived dendritic cells phagocytosed MTB H37Rv (Multiplicity of infection 10, infectivity: 46.89%), the CD1b expression level decreased slowly. Since this was just a live MTB-mediated phenomenon, it was not detected from heat-killed MTB or mycolic acid, which is a unique antigen of MTB. We confirmed that the phosphorylation of CD1b molecules using 2D electrophoresis with staining could phosphorylate and induce the presentation of the lipid antigen using the phagocytosis assay.

• Biomolecules & Therapeutics
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• v.18 no.2
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• pp.211-218
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• 2010

Acanthopanax koreanum Nakai (Araliaceae) is a medicinal plant indigenous to Korea. The root and stem barks of Acanthopanax species have been used as a tonic and sedative as well as in the treatment of rheumatism and diabetes. In our study, three lignans, eleutheroside E (EE), tortoside A (TA), and syringaresinol (SY), were isolated from the stem and root of A. koreanum in an effort to study the immunomodulating effect. We treated natural killer cells and dendritic cells with lignans (EE, TA, or SY), and analyzed their cytokine (IL-12 and IFN-${\gamma}$) secretion. EE, TA, or SY markedly enhanced IL-12 secretion in mouse lymphoid (DC1) and myeloid type (DC2.4) dendritic cells after 48 hr of treatment. There were no significant differences in the cytokine stimulatory effects between EE, TA, or SY. Moreover, treatment of EE, TA, or SY significantly induced IFN-${\gamma}$ secretion by human NK cells (NK92MI) confirmed by ELISA assay. This study suggests that lignans from A. koreanum modulate cytokines, and that such modulation may provide the mechanism of action for many of their therapeutic effects.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2665-2669
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• 2015

CD4+CD25+regulatory T cells (Tregs) play a key role in regulation of immnue response and maintenance of self-tolerance. Studies have found Tregs could suppress tumor-specific T cell-mediated immune response and promote cancer progression. Depletion of Tregs can enhance antitumor immunity. Dendritic cells (DCs) are professional antigen-presenting cells and capable of activating antigen-specific immune responses, which make them ideal candidate for cancer immunotherapy. Now various DC vaccines are considered as effective treatment for cancers. The aim of this study was to evaluate variation of Tregs in BALB/C mice with hepatocellular carcinoma and investigate the interaction between tumor-derived Tregs, effector T cells (Teff) and splenic DCs. We found the percentages of Tregs/CD4+ in the peripheral blood of tumor-bearing mice were higher than in normal mice. Tumor-derived Tregs diminished the up-regulation of costimulatory molecule expression on splenic DCs, even in the presence of Teff cells and simultaneously inhibited IL-12 and $TNF-{\alpha}$ secretion by DCs.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.607-613
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• 2003

Dendritic cells (DCs) play an essential role in a variety of immune reactions involving $CD4^+$ T cells and have been used to enhance tumor-specific immune responses. Immunosuppression in patients with cancer includes the downregulation of function and number of DCs. Although DCs have been studied, the apoptosis of Des induced by anticancer drugs for chemotherapy remains largely uncharacterized. This study demonstrated that GM-CSF protects DCs from 5-fluorouracil (5-FU) or mitomycin C-induced apoptosis. After 6 - 10 days culture, DCs were characterized by specific surface marker, CD11c and MHC class II. MTT assay revealed that GM-CSF significantly enhanced the viability of DCs treated with 5-FU or mitomycin C. The percentage of dead cells of DCs was determined by cell size using FACScan and GM-CSF was clearly effective. However, GM-CSF did not increase the expression of MHC class II on viable DCs gated, suggesting that GM-CSF may differentially regulate critical factors involved in the function of DCs. For the quantitative analysis of apoptosis, annexin V-FITC staining was performed. 5-FU induced the apoptosis of DCs and GM-CSF significantly protects DCs from 5-FU-induced apoptosis. Taken together, the results in this study that GM-CSF has an anti-apoptosis effect on DCs may provide patients with cancer with clinical benefits to overcome the immunosuppression induced by the decrease of number and functional insufficiency of DCs.

• IMMUNE NETWORK
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• v.6 no.4
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• pp.199-203
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• 2006

Background: Eckol purified from Ecklonia cava, a brown alga has been known to have cytoprotective effects on some cell lines against oxidants and ionizing radiation. However, there is no study about the effects of eckol on immune cells. Methods: Bone marrow (BM)-derived dendritic cells (DCs) were used to demonstrate the immunomodulatory effects of eckol on DCs, such as viability, the expression of surface markers, allogeneic stimulating capacity using MTI, flow cytometric, $^3H$-thymidine incorporation assay. Results: Eckol did protect DCs against cytokine withdrawal-induced apoptosis in a concentration dependent manner based on MTT assay. And also, it increased the expression of MHC class II and CD86 (B7.2) molecules, maturation markers, on the surface of viable DCs gated in FACS analysis. Furthermore, eckol-treated DCs stimulated the proliferation of allogeneic $CD4^+$ T lymphocytes compared to imDCs in $^3H$-thymidine incorporation assay. $CD4^+$ T lymphocytes activated with eckol-treated DCs produced the larger amount of IFN-${\gamma}$ and IL-4 than those cells with imDCs. Conclusion: Taken together, we demonstrate in this study that eckol, a pure compound of Ecklonia cava, may modulate the immune responses through the phenotypic and functional changes of DCs.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.471-479
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• 2023

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.

• BMB Reports
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• v.48 no.3
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• pp.178-183
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• 2015

Dendritic cells play an important role in determining whether na${\ddot{i}}$ve T cells mature into either Th1 or Th2 cells. We determined whether heat-shock protein X (HspX) purified from Mycobacterium tuberculosis regulates the Th1/Th2 immune response in an ovalbumin (OVA)-induced murine model of asthma. HspX increased interferon-gamma, IL-17A, -12 and transforming growth factor (TGF)-${\beta}$ production and T-bet gene expression but reduced IL-13 production and GATA-3 gene expression. HspX also inhibited asthmatic reactions as demonstrated by an increase in the number of eosinophils in bronchoalveolar lavage fluid, inflammatory cell infiltration in lung tissues, airway luminal narrowing, and airway hyper-responsiveness. Furthermore, HspX enhanced OVA-induced decrease of regulatory T cells in the mediastinal lymph nodes. This study provides evidence that HspX plays critical roles in the amelioration of asthmatic inflammation in mice. These findings provide new insights into the immunotherapeutic role of HspX with respect to its effects on a murine model of asthma.