• Clinical and Experimental Pediatrics
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• v.52 no.12
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• pp.1348-1357
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• 2009

Purpose:The aims of this study were to identify the clinical characteristics and determine the changes in the expression of cytokines and apoptosis-related genes in children with infectious mononucleosis. Methods:Serological examinations of 15 pediatric patients diagnosed with infectious mononucleosis were performed prospectively. Peripheral blood from the patients was used to compare the composition of T cell subsets, cytokines, Epstein-Barr virus (EBV) DNA, and the expression of apoptosis-related genes with those in 10 healthy children. Results:Mean age of the patient group was $5.7{\pm}3.4$ (range, 3-9) years, and the male-to-female ratio was 1.5:1. Fever, sore throat, pharyngitis/tonsillitis, and cervical lymph node enlargement were the most common symptoms and signs. The proportions of CD3+ T cells, CD8+ suppressor cells, and CD56+ natural killer (NK) cells were higher in the patient group than in the control group (P<0.01). The IL-2, IL-6, and interferon $(INF)-{\gamma}$ levels were higher in the early symptomatic period (P<0.01). Mean amount of EBV DNA in the patients was $10^{2.38}copies/{\mu}g$, and the amount was the highest at the beginning of the symptomatic period and normalized during the convalescent phase. Bcl-2 expression increased during the initial phase, while Bax expression increased during the convalescent phase. Further, FasL expression increased 1 week after symptom presentation and decreased during the convalescent phase. There was no significant change in Fas expression. Conclusion:We analyzed the clinical characteristics and changes in the expression ofcytokines and apoptosis-related genes in the patients with infectious mononucleosis.

• 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.

• Herbal Formula Science
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• v.20 no.2
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• pp.13-28
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• 2012

Objectives : The present study aimed to investigate the pharmacological activity of water and ethanol (EtOH) extracts from Socheongnyong-tang (SCNT) on inflammation and its related disease. Methods : The cells were treated with nontoxic concentrations of water and EtOH extract from SCNT in BEAS-2B, HaCaT, RAW 264.7 and 3T3-L1 cells. These cells were stimulated by tumor necrosis facter (TNF)-${\alpha}$, TNF-${\alpha}$/interferon (IFN)-${\gamma}$, and lipopolysaccharide (LPS), respectively. 3T3-L1 cells were differentiated by insulin. After incubation, supernatant were collected and biological indicator measured by enzyme-linked immunosorbent assay. Results : Our results indicate that the water and EtOH extract of SCNT significantly inhibited the production of regulated on activation normal T-cell expression and secreted (RANTES) by treatment of TNF-${\alpha}$ in BEAS-2B cell, and significantly reduced the production of RANTES and macrophage-derived chemokine increased by treatment of TNF-${\alpha}$/IFN-${\gamma}$ in HaCaT cell. Moreover, those extracts significantly decreased the activity of nitric oxide and prostaglandin $E_2$ in LPS-induced RAW 264.7, and significantly inhibited the increased activity of glycerol-3-phosphate dehydrogenase and expression of leptin induced by differentiation in 3T3-L1 cell. Conclusions : These results indicate that both water and EtOH extract of SCNT has powerful effects on inflammation and its related disease. Therefore, SCNT can be developed as a potential pharmacological agent related various diseases. Although the significant effects were observed in both SCNT water and EtOH extract, the EtOH extract was more effective on most experiments than its water extract. Taken together, these findings indicate that the SCNT EtOH extract may have more potential pharmacological agent.

• 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.16 no.6
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• pp.904-910
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• 2006

Dendritic cells (DCs) are the only antigen presenting cells (APCs) capable of initiating immune responses, which is crucial for priming the specific cytotoxic T lymphocyte (CTL) response and tumor immunity. Upon activation by DCs, CD4+ helper T cells can cross-prime CD8+ CTLs via IL-12. However, recently activated DCs were described to prime in vitro strong T helper cell type 1 $(Th_1)$ responses, whereas at later time points, they preferentially prime $Th_2$ cells. Therfore, we examined in this study the optimum kinetic state of DCs activation impacted on in vivo priming of tumor-specific CTLs by using ovalbumin (OVA) tumor antigen model. Bone-marrow-derived DCs showed an appropriate expression of surface MHC and costimulatory molecules after 6 or 7-day differentiation. The 6-day differentiated DCs pulsed with OVA antigen for 8 h (8-h DC) and followed by restimulation with LPS for 24 h maintained high interleukin (IL)-12 production potential, accompanying the decreased level in their secretion by delayed re-exposure time to LPS. Furthermore, immunization with 8-h DC induced higher intracellular $interferon(IFN)-{\gamma}+/CD8+T$ cells and elicited more powerful cytotoxicity of splenocytes to EG7 cells, a clone of EL4 cells transfected with an OVA cDNA, than immunization with 24-h DC. In the animal study for the evaluation of therapeutic or protective antitumor immunity, immunization with 8-h DC induced an effective antitumor immunity against tumor of EG7 cells and completely protected mice from tumor formation and prolonged survival, respectively. The most commonly used and clinically applied DC-based vaccine is based on in vitro antigen loading for 24 h. However, our data indicated that antigen stimulation over 8 h decreased antitumor immunity with functional exhaustion of DCs, and that the 8-h DC would be an optimum activation state impacted on in vivo priming of tumor-specific CTLs and subsequently lead to induction of strong antitumor immunity.

• Journal of Life Science
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• v.23 no.1
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• pp.63-68
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• 2013

The effect of black garlic extract on the activation of spleen cells from a C57BL6 mouse was investigated to examine immune activities of of fermented black garlic containing a variety of bioactive substances. xtract obtained from the concentration of commercial Namhae black garlic was used for the analysis of immune activities. Treatment with the extract increased the expression of interleukin-2 (IL-2) cytokine. The simultaneous administration of the extract plus lipopolysaccharide (LPS) increased the expression of IL-2, tumor necrosis factor (TNF)-${\alpha}$, and interferon (IFN)-${\gamma}$ compared with that of a control group. This result suggests that cellular immunity can be induced by macrophages, resulting in the expression of T lymphocytes and T helper type 1 (Th1) cells. In addition, treatment with the extract increased the late response of IL-6 cytokines, and the extract plus LPS augmented the expression of IL-4 and IL-6 compared with that of an LPS-treated group. Meanwhile, the extract plus LPS decreased the late response of IL-10, suggesting that humoral immunity can be activated by stimulating B lymphocytes, suppressing cellular immunity, and effectively modulating the conversion into humoral immune responses. These findings demonstrate that the black garlic extract activates Th1 and Th2 cells by stimulating T lymphocytes in mouse spleen cells and leads to immunomodulation by activating cellular and humoral immune responses of the immune system.

• 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.

• Journal of Gastric Cancer
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• v.7 no.3
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• pp.167-173
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• 2007

Purpose: Mistletoe (Viscum album L.) extract is one of the most widely used agents in alternative cancer therapeutic regimens in Europe. This study was conducted to determine the effect of mistletoe extract on immune function in gastric cancer patients. Materials and Methods: Ten patients that had undergone a curative gastrectomy were enrolled in the prospective study. ABNOBAviscum $Q^{(R)}$ was injected subcutaneously three times a week from postoperative-day 7 to week 16 with an increasing dose. All of the patients simultaneously received chemotheraphy with mitomycin, oral 5-FU and a cisplatin regimen. The WBC count, differential count, lymphocyte/WBC ratio and the level of cytokines (IL-$1{\beta}$, IL-2, IL-6, IFN-$\gamma$, TNF-$\alpha$) were checked in the peripheral blood preoperatively, at postoperative week 8 and at postoperative week 16. Results: The WBC and neutrophil counts significantly decreased after treatment on week 8 and week 16 (P=0.001), but the total eosinophil count was slightly increased (P=0.15). The total lymphocyte count also decreased during treatment but the lymphocyte/WBC ratio was slightly increased without statistical significance (P=0.91). The cytokine levels did not significantly change during treatment. Conclusion: It is somewhat difficult to determine the direct effect of mistletoe therapy on immune function as the effect may be compromised by the concurrent chemotherapy. It can be assumed that the slightly increased lymphocyte/WBC ratio and eosinophil count may be a result of the immunomodulatory effect of the mistletoe extract.

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.115-122
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• 2012

Objectives : This study evaluated activities and ingredient contents concerning extracts according to extraction solvents of Insampaedok-san (IS, Renshen bai du-san). Methods : The herbal constituents of IS were extracted with water and 70% ethanol at $100^{\circ}C$ for 2 hr. Using the HPLC system, the six ingredient contents of different solvent extracts of IS were analyzed. The nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) production and proinflammatory cytokines were measured in RAW264.7 cells stimulated with lipopolysaccharide (LPS). The macrophage-derived chemokine (MDC/CCL22) and regulated on activation normal T-cell expression and secreted (RANTES/CCL5) production were measured in HaCaT and BEAS-2B cells stimulated tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$). The activities of glycerol-3-phosphate dehydrogenase (GPDH) and leptin level were measured in 3T3-L1 cells. Results : The calibration curves showed good linearity ($r^2$=1.0000) for different concentration ranges. The contents of liquiritin, naringin, hesperidin, neohesperirin and glycyrrizin in 70% ethanol extracts of IS were relatively higher than that of water extract, however the content of ferulic acid in 70% ethanol and water extract of IS were similar. The extraction solvents of water and 70% ethanol were evaluated inhibitory effect on the production of NO, $PGE_2$, TNF-${\alpha}$ and IL-6 in RAW 264.7 cells. Their extractions were inhibitory effect on production of MDC/CCL22 and RANTES/CCL5 in HaCaT cell and BEAS-2B cell, respectively. In addition, evaluated reduced on GPDH activity and leptin level in 3T3-L1 preadipocyte cell. Conclusions : Our results suggest that IS extracts were inhibitory effects of disease such as inflammation, allergies and obesity.

• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.449-458
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• 2003

Background : The poor prognostic factors of far-advanced pulmonary tuberculosis(FAPTB) are lymphocytopenia in the peripheral blood(PB)(< $1,000/mm^3$) and $T_4$-cell count ${\leq}500/mm^3$. However, the cause of PB lymphocytopenia in FAPTB is unclear. The aim of this study was to analyze the lymphocyte proportion and cytokines of the bone marrow(BM) in FAPTB patients with peripheral lymphocytopenia in order to clarify whether the limiting step of the lymphocytopenia occurs in production, differentiation, or circulation. Methods : This study included patients with FAPTB between August 1999 and August 2002 who visited Gachon Medical School Gil Medical Center. The exclusion criteria were old age(${\geq}65years$), cachexia or a low body weight, shock, hematologic diseases, or BM involvement of tuberculosis. The distributions of cells in PB and BM were analyzed and compared to the control group. The interleukin(IL)-2, IL-7, IL-10, TNF-${\alpha}$, Interferon-${\gamma}$, and TGF-${\beta}$ levels in the BM were measured by ELISA. Result : Thirteen patients(male : female=9:4) were included and the mean age was $42{\pm}12$years. The proportion and count of the lymphocytes in the PB were significantly lower in the FAPTB group ($7.4{\pm}3.0%$, $694{\pm}255/mm^3$ vs. $17.5{\pm}5.8%$, $1,377{\pm}436/mm^3$, each p=0.0001 and 0.002). The proportion of immature lymphocyte in the BM showed a decreasing trend in the FAPTB group($9{\pm}4%$ vs. $12{\pm}3%$, p=0.138). The IL-2($26.0{\pm}29.1$ vs. $112.2{\pm}42.4pg/mL$, p=0.001) and IL-10($3.4{\pm}4.7$ vs. $12.0{\pm}8.0pg/mL$, p=0.031) levels in the BM were significantly lower in the FAPTB group than those in control. The levels of the other cytokines in FAPTB group and control were similar. Conclusion : These results suggest that the cause of lymphocytopenia in PB is associated with a abnormality IL-2 and IL-10 production in the BM. More study will be needed to define the mechanism of a decreased reservoir in BM.