• Korean Journal of Food Science and Technology
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• v.50 no.4
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• pp.444-450
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• 2018

Dendritic cells (DCs) are potent antigen-presenting cells that play a pivotal role in modulating both innate and adaptive immunity. This study examined the immunomodulatory activities of hot-water extracts of bee pollen (BPW) in bone-marrow derived DCs (BMDC) and mice splenocytes. BMDCs isolated from mice were treated with 250 and $500{\mu}g/mL$ BPW for 24 h. BPW, up to $500{\mu}g/mL$, did not display any cellular toxicity against BMDCs. In fact, it functionally induced BMDC activation via augmentation of CD80, CD86, and major histocompatibility complex (MHC) class I/II expression and pro-inflammatory cytokine (tumor necrosis factor; $TNF-{\alpha}$, interleukin; IL-6, and $IL-1{\beta}$) production. Interestingly, BPW treatment significantly increased the production of interferon $(IFN)-{\gamma}$ in splenocytes, suggesting its possible contribution to Th1 polarization in immune response. Taken together, these findings suggest that BPW may regulate innate and adaptive immunity via DC activation and Th1 polarization in immune responses.

• Food Science of Animal Resources
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• v.31 no.5
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• pp.701-709
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• 2011

This study was performed to establish an effective extraction method of pig placenta extract that could be used for a putative functional food supplement with immunomodulatory effects. In the present study, we used different temperatures (4, 37, 60, 80, and $100^{\circ}C$) and different solvents (chloroform, NaOH, and phosphate buffered saline [PBS]) to extract the pig placenta. Among the different placenta extracts yielded by the different extraction methods, placenta extract (PE) in PBS at $80^{\circ}C$ for 30 min (referred to as PE-PBS80) showed a significant increase of nitric oxide production of up to 22.97 ${\mu}M/10^5$ cells at a 1 mg/mL dose (p<0.05 ) in J774A.1 cells than other extracts and control tested. Using PE-PBS80, further animal challenges were performed to identify the immune-enhanced effects. As a result, orally administered PE-PBS80 showed a significant increase in blood T and B cell activities and immunoglobulin (IgG and IgM) production. IgG and IgM levels increased to 41.53 mg/mL at a 20 mg dose on day 7 and to 27.38 mg/mL at a 10 mg dose on day 14, respectively (p<0.05). Furthermore, PE-PBS80 was also able to significantly enhance the immune modulator cytokine levels (p<0.05) compared to the control and vehicle treatments. Among the evaluated cytokines, the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) level increased to 28.89 pg/mL at extract doses of 20 and 50 mg, the interleukin-$1{\beta}$ (IL-$1{\beta}$) level increased to 21.52 pg/mL at extract doses of 10, 20, 50 and 75 mg and the interferon (IFN)-${\gamma}$ level increased to 18.24 pg/mL at extract doses of 10, 20, and 50 mg. Therefore, this study presents an effective method for extracting pig placenta extracts and also demonstrates that pig placenta extracts had significant immunomodulatory effects not only at the cellular level but also in a mouse model, suggesting that this material could be used as an excellent candidate functional food supplement.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.8
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• pp.1099-1106
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• 2016

The objective of this study was to evaluate the immunomodulatory activity of crude polysaccharide separated from Cudrania tricuspidata leaf. C. tricuspidata polysaccharide (CTP) was extracted by ethanol precipitation. Immunomodulation activity was tested in macrophage cells (RAW 264.7 and bone-marrow derived macrophage) and splenocytes. CTP treatment significantly increased cell proliferation up to $250{\mu}g/mL$ in both RAW 264.7 and bone-marrow derived macrophages. In this concentration range (below $250{\mu}g/mL$), nitric oxide and cytokine [tumor necrosis factor $(TNF)-{\alpha}$ and interleukin (IL)-6] production also significantly increased. Similarly, splenocyte proliferation dosedependently increased except for the $1,000{\mu}g/mL$ treated group. Regarding cytokine production activity in splenocytes, CTP treatment significantly increased production of Th 1 type cytokines [interferon $(IFN)-{\gamma}$] production but not Th 2 type cytokines (IL-4). Therefore, the results indicate that CTP may have a potential effect on immunomodulatory activity in various immune cells, and this is useful for development of immune enhancing adjuvant materials as a natural ingredient.

• Korean Journal of Food Science and Technology
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• v.49 no.5
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• pp.559-566
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• 2017

This aim of this study was to examine the immunomodulatory activities of crude polysaccharides from Perilla frutescens Britton var. acuta Kudo (PCP) in mouse bone marrow-derived dendritic cells (BMDC) and splenocytes. The immunomodulatory activity was determined by cell viability, nitric oxide (NO) production, cell surface marker expression (CD 80/86 and MHC class I/II), and cytokine production in BMDC, and cell viability, and cytokine production in splenocytes. Cell proliferation and cytokine production (tumor necrosis factor; TNF-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, and IL-12) tested in BMDC were significantly increased by PCP treatment. Additionally, the cell surface markers (CD 80/86, MHC class I/II) were highly increased by PCP treatment. For cytokine production in splenocytes, PCP treatment significantly increased the production of Th 1 cytokines [IL-2 and interferon (IFN)-${\gamma}$], but not Th 2 cytokines (IL-4). Therefore, PCP can induce immune cell activation and is a potential candidate for the development of nutraceuticals to boost the immune system.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.4
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• pp.377-383
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• 2021

Purpose: We investigated the association of effector memory (EM) CD8⁺ T cell and CD4⁺ T cell immunity with metabolic syndrome (MS). Methods: Surface and intracellular staining of peripheral blood mononuclear cells was performed. Anti-interleukin-7 receptor-alpha (IL-7Rα) and CX3CR1 antibodies were used to stain the subsets of EM CD8⁺ T cells, while anti-interferon-gamma (IFN-γ), interleukin-17 (IL-17), and forkhead box P3 (FOXP3) antibodies were used for CD4⁺ T cell subsets. Results: Of the 47 obese children, 11 were female. Children with MS had significantly higher levels of serum insulin (34.8±13.8 vs. 16.4±6.3 µU/mL, p<0.001) and homeostasis model assessment of insulin resistance (8.9±4.1 vs. 3.9±1.5, p<0.001) than children without MS. Children with MS revealed significantly higher frequencies of IL-7Rα^low CD8⁺ T cells (60.1±19.1% vs. 48.4±11.5%, p=0.047) and IL-7Rα^lowCX3CR1⁺ CD8⁺ T cells (53.8±20.1% vs. 41.5±11.9%, p=0.036) than children without MS. As the serum triglyceride levels increased, the frequency of IL-7Rα^lowCX3CR1⁺ and IL-7Rα^highCX3CR1^- CD8⁺ T cells increased and decreased, respectively (r=0.335, p=0.014 and r=-0.350, p=0.010, respectively), in 47 children. However, no CD4⁺ T cell subset parameters were significantly different between children with and without MS. Conclusion: In obese children with MS, the changes in immunity due to changes in EM CD8⁺ T cells might be related to the morbidity of obesity.

• The Korea Journal of Herbology
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• v.34 no.2
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• pp.41-47
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• 2019

Objectives : A traditional herbal prescription, Kyung-Ok-Ko (KOK), has long been used in oriental medicine as an invigorant for age-related diseases, such as amnesia and stroke. However, the beneficial value of KOK for immune responses is largely unknown. Based on the above mentioned effects of KOK, other previous reports, and its use in traditional medicine, we hypothesized that KOK displays beneficial effects against methotrexate (MTX)-induced immune suppression. Methods : We investigated the effects of KOK (0.6 g/kg/day, oral (p.o.)) on deteriorated immunity caused by MTX (2 mg/kg/day, p.o.) in an immune suppression mouse model. MTX was fed to mice once a day for 7 days. After the immune responses of the mice deteriorated by MTX treatment, KOK in water was fed to the mice once a day for 14 days. We then measured the expression levels of various cytokines, such as T helper cell (Th1, Th2) cytokines, and the number of immune cells, such as spleen T cells, B cells, and macrophages. Results : The data showed that MTX decreased Th1 profiles (interferon $(IFN)-{\gamma}$, interleukin (IL)-2, IL-12) and the number of immune cells, and increased Th2 profiles (IL-4, IL-5, IL-13), which were normalized significantly by post-administration of KOK. However, there was no significant difference in body-weight gain between MTX- and KOK-treated mice. Conclusion : These results indicate that KOK has immune-enhancing functions and reduces immunotoxicity of MTX, suggesting that supplementation with KOK will improve immune responses clinically and be useful for the prevention of immune-related diseases.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.336-344
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• 2004

Background : Immunotherapy for cancer has not been successful because of several obstacles in tumor and its environment. Inappropriate secretions of cytokines and growth factors by tumors cause substantial changes in the immune responses against tumors, affording the tumors some degree of protection from immune attack. Uteroglobin (UG, Clara cell secretory protein) has been known to have anti-inflammatory, immunomodulatory and anti-cancer activities. However, in lung cancer cells, UG expression is decreased. This study investigated the role of UG in the immunomodulation of lung cancer. Methods : The UG protein was overexpressed by Adenovirus(Ad)-UG transduction in non-small cell lung cancer cell lines. The concentration of Prostaglandin $E_2$ ($PGE_2$) was measured by Enzyme Immunoassay (EIA). Peripheral blood mononuclear cells (PBMC) from whole blood were prepared with Ficoll. PBMC were cultured in RPMI 1640, supernatant of A549, or A549 with UG or NS-398. Concentration of Th 1 type and Th 2 type cytokines from PBMC were measured by ELISA. Results : UG suppressed $PGE_2$, Cyclooxygenase-2 (COX-2) product. Both Th1 type such as Interleukin-2 (IL-2), Interferon-${\gamma}$ (IFN-${\gamma}$) and Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and Th2 type cytokines such as IL-10 and Tumor growth factor-${\beta}$ (TGF-${\beta}$) were increased when PBMC were cultured with supernatant of non small lung cancer cells. UG and COX-2 inhibitor, NS-398 induced normal immune response of PBMC. Although Th 1 type cytokines were increased, Th 2 type cytokines were reduced by UG. Conclusion : UG suppressed PGE2, COX-2 product. Supernatant of NSCLC induced imbalance of immune response of PBMC. However, UG reversed this imbalance. These results suggest that UG may be used in the development of immunotherapy for lung cancer.

• Applied Biological Chemistry
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• v.51 no.2
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• pp.142-147
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• 2008

Nuruk is the Korean traditional Koji that contains various microorganisms and has been used to make the traditional fermented foods including alcoholic beverages. Rhizopus oryzae KSD-815 was isolated from the alcohol-fermenting Nuruk used for manufacturing traditional alcohol. In this study, the authors reported the isolation and identification of four lipids from the Nuruk (Rhizopus oryzae KSD-815) that inoculated wheat with Rhizopus oryzae KSD-815. The dried and powdered Nuruk (Rhizopus oryzae KSD-815) were extracted three times at room temperature with 80% aqueous MeOH. The extracts were partitioned with EtOAc, n-BuOH, and water, successively. The EtOAc extract was suspended in 80% MeOH and partitioned repeatedly with n-hexane. From the n-hexane fraction, four lipids were isolated through the repeated silica gel and ODS column chromatographies. According to the results of physico-chemical data including NMR, GC and MS, the chemical structures of the compounds were determined as linolenic acid methyl ester (1), palmitic acid methyl ester (2), linoleic acid (3), palmitic acid (4). Cytotoxicity was evaluated in huamn breast cancer cells, MDA-MB-231 and human hepatocarcinoma, SK-HEP-1 cells using MTT assay. Exposure of compounds 1 and 3 led to a dose-dependent inhibition of cell viability in both cancer cell lines. In addition, treatment of RAW264.7 cells with compound 3 caused inhibition of lipopolysaccharide/interferon-${\gamma}$-induced nitric oxide production.

• Korean Journal of Food Science and Technology
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• v.40 no.5
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• pp.574-579
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• 2008

Propolis is the generic term for the resinous substance collected by honey bees from a variety of plant sources. In this study, we have assessed the immunomodulatory properties of propolis (P) and fermented-propolis (FP) in BALB/c mice. Mice were subjected to gavage once a day (for 14 days) with 50, 100, 200 mg/kg body weight P, FP, or vehicle. Lymphocytes were isolated from the spleen and mesenteric lymph nodes (MLN) and the immune cell proportions, proliferative activities, and cytokine production were evaluated. The P- and FP-administration induced similar, but differential, alterations in the percentage of immune cell populations and their biological functions, including cytokine production and NK cell cytotoxicity. The proportion of$ CD4^+$ and $CD8^+$ T cells in the spleen was increased slightly in the P- and FP-administered mice as compared to the vehicle-treated mice. In MLN, the percentage of $CD4^+$ T cells was increased significantly in the 200 mg/kg P-treated mice. The mice which were treated with P and FP evidenced significantly increased interferon-$\gamma$ and interleukin-4 production in concanavalin A-stimulated splenocytes, whereas the production of theses cytokines was not shown to be induced by P-treatment. In addition, NK cell activity was also increased dramatically by the administration of P and FP. Collectively, these findings showed that P and FP are wide-spectrum immunomodulators, which may modulate both innate and adaptive immune responses.

• Journal of Life Science
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• v.24 no.8
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• pp.851-859
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• 2014

The present study was designed to investigate whether ethanol extracts of Sophora flavescens (GS), Glycyrrhiza uralensis (GC), Dictamnus dasycarpus (BSP), and their mixtures (GGB-1, -2, -3, and -4) inhibit 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in a mouse model. DNCB was topically applied on the dorsal surface of Balb/c mice to induce AD-like skin lesions. The pathological phenotypes of AD, such as erythema, ear thickness, edema, scabs, and discharge, were significantly decreased in the GGB (DNCB + GS:GC:BSP = 3:1:1 mixture)-1-treated groups compared with the other treated groups. The weight of the spleen in immune organs was significantly decreased in the GGB-1-treated groups, whereas the weight of the liver in a control group was similar to that of the groups treated with the samples. Furthermore, toluidine blue staining analysis, a method used to specifically identify mast cells, showed that master cell infiltration into the dermis of the GGB-1-treated group was significantly decreased. The immunoglobulin E concentration was lower in the GGB-1-treated group. In addition, the levels of inflammatory cytokines (interferon-${\gamma}$, interleukin-1, 4, 5, 6, and 13, $1{\beta}$, and tumor necrosis factor-${\alpha}$) were also significantly reduced in the GGB-1-treated group. Taken together, these results suggest that a mixture of GS, GC, and BSP in a proportion of 3:1:1 (GGB-1) may contribute to the relief of AD symptoms and may be considered an excellent candidate for an AD therapeutic drug.