• Journal of Ginseng Research
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• v.43 no.1
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• pp.49-57
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• 2019

Background: Korean Red Ginseng (KRG; Panax ginseng Meyer) is a widely used medicinal herb known to exert various immune modulatory functions. KRG and one of its purified components, ginsenoside Rg3, are known to possess anti-inflammatory activities. How they impact helper T cell-mediated responses is not fully explored. In this study, we attempted to evaluate the effect of KRG extract (KRGE) and ginsenoside Rg3 on Th1 cell responses. Methods: Using well-characterized T cell in vitro differentiation systems, we examined the effects of KRGE or enhanced Rg3 on the Th1-inducing cytokine production from dendritic cells (DC) and the naïve $CD4^+$ T cells differentiation to Th1 cells. Furthermore, we examined the change of Th1 cell population in the intestine after treatment of enhanced Rg3. The influence of KRGE or enhanced Rg3 on Th1 cell differentiation was evaluated by fluorescence-activated cell sorting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. Results: KRGE significantly inhibited the production level of IL-12 from DCs and subsequent Th1 cell differentiation. Similarly, enhanced Rg3 significantly suppressed the expression of interferon gamma ($IFN{\gamma}$) and T-bet in T cells under Th1-skewing condition. Consistent with these effects in vitro, oral administration of enhanced Rg3 suppressed the frequency of Th1 cells in the Peyer's patch and lamina propria cells in vivo. Conclusion: Enhanced Rg3 negatively regulates the differentiation of Th1 cell in vitro and Th1 cell responses in the gut in vivo, providing fundamental basis for the use of this agent to treat Th1-related diseases.

• IMMUNE NETWORK
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• v.24 no.2
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• pp.14.1-14.26
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• 2024

The inflammatory response during cutaneous leishmaniasis (CL) involves immune and non-immune cell cooperation to contain and eliminate Leishmania parasites. The orchestration of these responses is coordinated primarily by CD4⁺ T cells; however, the disease outcome depends on the Th cell predominant phenotype. Although Th1 and Th2 phenotypes are the most addressed as steers for the resolution or perpetuation of the disease, Th17 cell activities, especially IL-17 release, are recognized to be vital during CL development. Th17 cells perform vital functions during both acute and chronic phases of CL. Overall, Th17 cells induce the migration of phagocytes (neutrophils, macrophages) to the infection site and CD8⁺ T cells and NK cell activation. They also provoke granzyme and perforin secretion from CD8⁺ T cells, macrophage differentiation towards an M2 phenotype, and expansion of B and Treg cells. Likewise, immune cells from the inflammatory infiltrate have modulatory activities over Th17 cells involving their differentiation from naive CD4⁺ T cells and further expansion by generating a microenvironment rich in optimal cytokines such as IL-1β, TGF-β, IL-6, and IL-21. Th17 cell activities and synergies are crucial for the resistance of the infection during the early and acute stages; however, if unchecked, Th17 cells might lead to a chronic stage. This review discusses the synergies between Th17 cells and the inflammatory infiltrate and how these interactions might destine the course of CL.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.11
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• pp.1621-1628
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• 2015

The immune system plays an important role in maintaining and protecting human health. In the present study, comparison of immuno-modulatory activities between polysaccharides (SFP) and ethanol (SFE) extracts separated from Sargassum fulvellum in macrophages and murine splenocytes were investigated. Immuno-modulatory activities of macrophages were estimated based on cell proliferation, nitric oxide (NO), inducible NO synthase (iNOS), and cytokine production in RAW 264.7 macrophage cells, and lipopolysaccharide was used as a positive control. SFP and SFE treatment did not affect cytotoxicity in RAW 264.7 macrophage cells, and SFP treatment significantly increased NO and cytokine production ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$), whereas SFE did not contribute to the increase in NO and cytokine production. In the case of splenocytes, SFP treatment increased splenocyte proliferation and also highly increased production of Th-1 type cytokines (IL-2 and $IFN-{\gamma}$) than those of SFE. Through this study, we confirmed that immuno-modulatory activities of Sargassum fulvellum may be due to polysaccharide extracts and this can be a potential nutraceutical.

• Preventive Nutrition and Food Science
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• v.7 no.3
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• pp.332-345
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• 2002

It is a recent observation that about 80 per cent of the body's immune system is localized in the gastrointestinal tract. This explains to a large extent why eating right is important for the modulation the immune response and prevention of disease. In addition it is increasingly recognized that the body has an important digestive system also in the lower gastrointestinal tract where numerous important substances are released by microbial enzymes and absorbed. Among these substances are short chain fatty acids, amino acids, various carbohydrates, poly-amines, growth factors, coagulation factors, and many thousands of antioxidants, not only traditional vitamins but numerous flavonoids, carotenoids and similar plant- and vegetable produced antioxidants. Also consumption of health-promoting bacteria (probiotics) and vegetable fibres (prebiotics) from numerous sources are known to have strong health-promoting influence. It has been calculated that the intestine harbours about 300,000 genes, which is much more than the calculated about 60,000 for the rest of the human body, indicating a till today totally unexpected metabolic activity in this part of the GI tract. There are seemingly several times more active enzymes in the intestine than in the rest of the body, ready to release hundred thousand or more of substances important for our health and well-being. In addition do the microbial cells produce signal molecules similar to cytokines but called bacteriokines and nitric oxide, with provide modulatory effects both on the mucosal cells, the mucosa- associated lymphoid system (MALT) and the rest of the immune system. Identification of various fermentation products, and often referred to as synbiotics, studies of their role in maintaining health and well-being should be a priority issue during the years to come.

• Journal of Radiation Industry
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• v.10 no.1
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• pp.7-12
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• 2016

Ikaros, a transcription factor containing zinc-finger motif, has known as a critical regulator of hematopoiesis in immune system. Ikaros protein modulates the transcription of target genes via binding to the regulatory elements of the genes promoters. However the regulatory function of Ikaros in other organelle except nuclear remains to be determined. This study explored radiation-induced modulatory function of Ikaros in cytoplasm. The results showed that Ikaros protein lost its DNA binding ability after LDIR (low-dose ionizing radiation) exposure. Cell fractionation and Western blot analysis showed that Ikaros protein was translocated into cytoplasm from nuclear by LDIR. This was confirmed by immunofluorescence assay. We identified Autotaxin as a novel protein which potentially interacts with Ikaros through in vitro protein-binding screening. Co-immunoprecipitation assay revealed that Ikaros and Autotaxin are able to bind each other. Autotaxin is a crucial enzyme generating lysophosphatidic acid (LPA), a phospholipid mediator, which has potential regulatory effects on immune cell growth and motility. Our results indicate that LDIR potentially regulates immune system via protein-protein interaction of Ikaros and Autotaxin.

• IMMUNE NETWORK
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• v.22 no.5
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• pp.41.1-41.16
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• 2022

The human antimicrobial peptide LL-37 has chemotactic and modulatory activities in various immune cells, including dendritic cells. Because of its characteristics, LL-37 can be considered an adjuvant for vaccine development. In this study, we confirmed the possible adjuvant activity of LL-37 in mucosal vaccine development against Middle East respiratory syndrome-coronavirus (MERS-CoV) by means of intranasal immunization in C57BL/6 and human dipeptidyl peptidase 4 (hDPP4)-transgenic (hDPP4-Tg) mice. Intranasal immunization using the receptor-binding domain (RBD) of MERS-CoV spike protein (S-RBD) recombined with LL-37 (S-RBD-LL-37) induced an efficient mucosal IgA and systemic IgG response with virus-neutralizing activity, compared with S-RBD. Ag-specific CTL stimulation was also efficiently induced in the lungs of mice that had been intranasally immunized with S-RBD-LL-37, compared with S-RBD. Importantly, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to reduced immune cell infiltration into the lungs after infection with MERS-CoV. Finally, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to enhanced protective efficacy, with increased survival and reduced body weight loss after challenge infection with MERS-CoV. Collectively, these results suggest that S-RBD-LL-37 is an effective intranasal vaccine candidate molecule against MERS-CoV infection.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.849-855
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• 2007

Atopic dermatitis is an allergic inflammatory skin disease caused by aberrant and overreactive immune responses including overactivation of $T_H2$ immune responses, high levels of IgE as well as proinflammatory cytokines and chemokines. We examined whether BHOSB, a traditional herbal medicine, has modulatory effects on various immunological factors related to pathogenesis of atopic dermatitis in ONCB treated NC/Nga mice. Oral administration of BHOSB at the concentration of 10.8 mg/mouse/day significantly inhibited the production of IgE compared with control, and the levels of IgG2a and IgG2b, but not IgG1, were also significantly reduced. Production of IL-6 and TNF-a was greatly decreased. The results from flowcytometry of peripheral blood mononuclear cells indicated that the percentages of C03+C069+ cells and C04+ were significantly decreased by BHOSB. Theses results suggested that BHOSB has suppressive effects on aberrant and overreactive immunological activities in ONCB-induced dermatitis mice of NC/Nga.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.309-314
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• 2016

Korean Red Ginseng (KRG) is a heat-processed ginseng developed by the repeated steaming and air-drying of fresh ginseng. Compared with fresh ginseng, KRG has been shown to possess greater pharmacological activities and stability because of changes that occur in its chemical constituents during the steaming process. In addition to anticancer, anti-inflammatory, and immune-modulatory activities, KRG and its purified components have also been shown to possess protective effects against microbial infections. Here, we summarize the current knowledge on the properties of KRG and its components on infections with human pathogenic viruses such as respiratory syncytial virus, rhinovirus, influenza virus, human immunodeficiency virus, human herpes virus, hepatitis virus, norovirus, rotavirus, enterovirus, and coxsackievirus. Additionally, the therapeutic potential of KRG as an antiviral and vaccine adjuvant is discussed.

• Korean Journal of Medicinal Crop Science
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• v.17 no.1
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• pp.54-60
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• 2009

This study was performed to improve immune activities of Rubus coreanus Miquel by encapsulation of nanoparticles. Immuno-activities of R. coreanus were investigated through aqueous extracts associated with process of water at $60^{\circ}C$. It showed high promotion of human B and T cells growth about 50%, compared to the case of other conditions. The secretion of IL-6 and TNF-${\alpha}$ was also enhanced as $2.44{\times}10^{-4}$pg/cell and $1.94{\times}10^{-4}$pg/cell, results by adding nano samples. NK cell activation was improved up to 29% higher than the conventional extraction process. The secretion of NO from macrophage showed 14.9 ${\mu}M$ on the nano-encapsulation process extracts, which was higher than others. The size of nanoparticles was in the range of 50${\sim}$300 nm, which can effect the penetration into the cells. It was clearly observed by real time confocal microscope.

• YAKHAK HOEJI
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• v.51 no.6
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• pp.482-489
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• 2007

Kaempferitrin, isolated from Kenaf (Hibiscus cannabinus), was examined to evaluate its modulatory effects on antigen-presenting cell functions of macrophages/monocytes such as phagocytosis of foreign materials, up-regulation of costimulatory molecules (CD40, CD80 and CD86), adhesion molecule activation, and antigen processing and presentation. Kaempferitrin strongly blocked up-regulation of CD40, CD80 and CD86, but not pattern recognition receptor (PRR) (e.g., TLR2). It also suppressed functional activation of CD29 (${\beta}1$-integrins), as assessed by cell-cell adhesion assay, required for T cell-antigen-presenting cell (APC) interaction. Furthermore, this compound did not block a simple activation of CD29, as assessed by cell-fibronectin adhesion assay. However, the compound did not diminish phagocytic uptake, an initial step for antigen processing, and ROS generation in RAW264.7 cells. In particular, to understand molecular mechanism of kaempferitrin-mediated inhibition, the regulatory role of LPS-induced signaling events was examined using immunoblotting analysis. Interestingly, this compound dose dependently suppressed the phosphorylation of $I{\kappa}B{\alpha}$, Src, Akt and Syk, demonstrating that it can negatively modulate the activation of these signaling enzymes. Therefore, our data suggested that kaempferitrin may be involved in regulating APC function-relevant immune responses of macrophages and monocytes by regulating intracellular signaling.