• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.6
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• pp.956-961
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• 2010

Tumor necrosis factor-alpha (TNF-${\alpha}$) is a major mediator of immuno-inflammatory activity. The purpose of this study is to investigate whether TNF-${\alpha}$ productions of mouse macrophage RAW 264.7 and human hepatocyte HepG2 are modulated by Artemisiae argi Folium water extract (AW), Lactobacillus pentosus-fermented Artemisiae argi Folium water extract (AFL), and Saccharomyces cerevisiae-fermented Artemisiae argi Folium water extract (AFS) for 3 h of incubation. Effect of AW on cell viability of HepG2 was also investigated. TNF-${\alpha}$ productions were measured by Enzyme-Linked Immnunosorbent Assay method and cell viability was measured by MTT assay. Both AFL and AFS significantly increased TNF-${\alpha}$ productions of RAW 264.7 at the concentration of 50, 100, and 200 ${\mu}g$/mL (p<0.05). Also, AFL and AFS significantly increased TNF-${\alpha}$ productions of HepG2 at the concentration of 50, 100, and 200 ${\mu}g$/mL (p<0.05). AW significantly increased TNF-${\alpha}$ production of HepG2 at the concentration of 100 and 200 ${\mu}g$/mL (p<0.05). AW did not show any cytotoxicity on HepG2 cells for 3 h. These results suggest that AFL, AFS, and AW have the immune-enhancing property related with its increasing effect on TNF-${\alpha}$ production of macrophage and hepatocyte.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.333-339
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• 2008

Korean ginseng (Panax ginseng C. A. Meyer) has been used as an important medicinal plant in the Orient for a long time. It has been claimed that ginseng has many beneficial bioactive effects on human health, such as antitumor, antistress, antiaging and enhancing immune functions. Red ginseng possibly have new ingredients converted during steaming and dry process from fresh ginseng. Kujeungkupo method which means 9 repetitive steaming and drying process was used for the processes of green tea, Polygonatum odoratum, and Rehmanniae radix preparata. In this study, ingredient conversion of ginseng by 9 repetitive steaming and drying process were investigated measuring conversion efficiency of brown materials, crude lipids, crude proteins and aromatic compounds. Brown materials, as an antioxidant, in red ginseng were produced through non-enzymatic reaction by heat. Repetitive steaming and drying treatments on ginseng root contiunously increased the content of brown materials and the chromaticity. Crude lipids were degraded by heat and converted into volatile aromatic ingredients. Crude lipids were degraded and decreased by 0.52% after the 5th and 7th. Crude proteins were also decomposed and converted to amino acid. Crude proteins after the 9th treatment were decreased by more than 85% as increased times of treatments. A bicyclogermacrene as aromatic material was decreased as increased treatment times, while but a aromatic caramel was increased.

• The Korean Journal of Mycology
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• v.44 no.4
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• pp.296-299
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• 2016

Lentinula edodes is an edible mushroom that contains a ${\beta}$-glucan called lentinan, which has antitumor and immune-enhancing properties. In the present study, the ${\beta}$-glucan contents of L. edodes mushrooms cultivated on sawdust with different nutritional supplements and fruiting temperatures were measured using a commercial ${\beta}$-glucan assay kit purchased from Megazyme (Bray, Ireland). The weight loss of sawdust media and the yield of fruiting bodies showed similar trends, but the yield was more closely associated with the nutritional supplements used than the weight loss of sawdust media was. The ${\beta}$-glucan contents of L. edodes were 39.5-42.1%, except in the bean curd refuse + $CaCl_2$ supplementation group (50.4%). Furthermore, the ${\beta}$-glucan content decreased with increasing temperatures and was 42.4% at a low fruiting temperature.

• The Journal of Korean Medicine
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• v.19 no.2
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• pp.420-438
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• 1998

Herba Xanthii(HX), Radix Xantluii(RX) and Fructus Xanthii(FX) is one of the oriental medicine that has been used for the treatment of such infectious diseases and tumors. However, the mechanism of the drug is not investigated much. This study was done to know the effects of HX, RX and FX extract on the such innate immunities as phagocytic function and reactive radical formtions from phagocytes and the such acquired immunities as humoral and cell-mediated immunities. The followings are the results obtained from this study: 1. HX2 and FX1 groups increases the in vivo phagocytic activity of mononuclear phagocytes. 2. HXB, RXB, RXC, FXB and FXC groups increase the in vitro phagocytic activities. 3. RXB group stimulated the macrophages to produce nitric oxide in the presence of $interferon-{\gamma}$ $(IFN-{\gamma})$. 4. HX and RX whole groups increased the luminol-amplified reactive oxygen intermediate production in vivo. 5. HX whole and RX1, FX2 groups increased the lucigenin-amplified reactive oxygen intennediate production in vivo. 6. HXC group only increased the luminol-amplified reactive oxygen intermediate production in vitro. 7. HXB, FXB and FXC groups increased the lucigenin-amplified reactive oxygen intermediate production in vitro. 8. HX2, RX1 and FX whole groups increased the hemolysin formations from B cells. 9. HX, RX and FX whole groups significantly increased the rosette forming cells from the spleen. 10. HX, RX and FX whole groups significantly decreased the delayed-type hypersensitivity measured by footpad swelling. The above results demonstrate that HX, RX and FX has enhancing effects on innate immunity selectively and decreasing effects on delayed-type hypersensitivity of cell-mediated immunity according to medicinal part and diluted condition. This immunomodulating effects of HX, RX and FX might be responsible for the treatment of immune-mediated disorders.

• Journal of Microbiology and Biotechnology
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• v.23 no.7
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• pp.1023-1030
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• 2013

Lipoteichoic acid (LTA), uniquely expressed on gram-positive bacteria, is recognized by Toll-like receptor 2 (TLR2) on not only antigen-presenting cells but also activated T cells. Therefore, it is reasonable to assume that LTA is acting on T cells. However, little is known about the effect of LTA on T-cell regulation. In the present study, we investigated the immunomodulatory effects of LTA on $CD4^+$ T cells. Effector $CD4^+$ T cells, induced after co-culture with S. aureus-pulsed dendritic cells, produced high levels of interferon-${\gamma}$, CD25, CD69, and TLRs 2 and 4. When effector $CD4^+$ T cells were treated with LTA, the expressions of the membrane-bound form of transforming growth factor (TGF)-${\beta}$ and forkhead box P3 increased. Coincidently, the proliferation of effector $CD4^+$ T cells was declined after LTA treatment. When TGF-${\beta}$ signaling was blocked by the TGF-${\beta}$ receptor 1 kinase inhibitor, LTA failed to suppress the proliferation of effector $CD4^+$ T cells. Therefore, the present results suggest that LTA suppresses the activity of effector $CD4^+$ T cells by enhancing TGF-${\beta}$ production.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.476-484
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• 2018

Background: Korean Red Ginseng (steamed and dried white ginseng, Panax ginseng Meyer) is well known for enhancing vital energy and immune capacity and for inhibiting cancer cell growth. Some clinical studies also demonstrated a therapeutic potential of ginseng extract for treating lung inflammatory disorders. This study was conducted to establish the therapeutic potential of ginseng saponins on the lung inflammatory response. Methods: From Korean Red Ginseng, 11 ginsenosides (Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1, Rg2, Rg3, and Rh2) were isolated. Their inhibitory potential and action mechanism were evaluated using a mouse model of lung inflammation, acute lung injury induced by intranasal lipopolysaccharide administration. Their anti-inflammatory activities were also examined in lung epithelial cell line (A549) and alveolar macrophage (MH-S). Results: All ginsenosides orally administered at 20 mg/kg showed 11.5-51.6% reduction of total cell numbers in bronchoalveolar lavage fluid (BALF). Among the ginsenosides, Rc, Re, Rg1, and Rh2 exhibited significant inhibitory action by reducing total cell numbers in the BALF by 34.1-51.6% (n = 5). Particularly, Re showed strong and comparable inhibitory potency with that of dexamethasone, as judged by the number of infiltrated cells and histological observations. Re treatment clearly inhibited the activation of mitogen-activated protein kinases, nuclear factor-${\kappa}B$, and the c-Fos component in the lung tissue (n = 3). Conclusion: Certain ginsenosides inhibit lung inflammatory responses by interrupting these signaling molecules and they are potential therapeutics for inflammatory lung diseases.

• BMB Reports
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• v.41 no.11
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• pp.814-819
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• 2008

Interleukin-32 (IL-32) induces a variety of proinflammatory cytokines and chemokines. The IL-32 transcript was reported originally in activated T cells; subsequently, it was demonstrated to be abundantly expressed in epithelial and endothelial cells upon stimulation with inflammatory cytokines. IL-32 is regulated robustly by other major proinflammatory cytokines, thereby suggesting that IL-32 is crucial to inflammation and immune responses. Recently, an IL-32$\alpha$-affinity column was employed in order to isolate an IL-32 binding protein, neutrophil proteinase 3 (PR3). Proteinase 3 processes a variety of inflammatory cytokines, including TNF$\alpha$, IL-$1{\beta}$, IL-8, and IL-32, thereby enhancing their biological activities. In the current study, we designed four PR3-cleaved IL-32 separate domains, identified by potential PR3 cleavage sites in the IL-32$\alpha$ and $\gamma$ polypeptides. The separate domains of the IL-32 isoforms $\alpha$ and $\gamma$ were more active than the intrinsic $\alpha$ and $\gamma$ isoforms. Interestingly, the N-terminal IL-32 isoform $\gamma$ separate domain evidenced the highest levels of biological activity among the IL-32 separate domains.

• IMMUNE NETWORK
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• v.14 no.6
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• pp.296-306
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• 2014

There is growing evidence that crosstalk between mantle cell lymphoma (MCL) cells and stromal microenvironments, such as bone marrow and secondary lymphoid tissues, promotes tumor progression by enhancing survival and growth as well as drug resistance of MCL cells. Recent advances in the understanding of lymphoma microenvironment have led to the identification of crucial factors involved in the crosstalk and subsequent generation of their targeted agents. In the present study, we evaluated the combinatory effect of blocking antibodies (Ab) targeting CXCR4 and VLA-4, both of which were known to play significant roles in the induction of environment-mediated drug resistance (EMDR) in MCL cell line, Jeko-1. Simultaneous treatment with anti-CXCR4 and anti-VLA-4 Ab not only reduced the migration of Jeko-1 cells into the protective stromal cells, but also enhanced sensitivity of Jeko-1 to a chemotherapeutic agent to a greater degree than with either Ab alone. These combinatorial effects were associated with decreased phosphorylation of ERK1/2, AKT and NF-${\kappa}B$. Importantly, drug resistance could not be overcome once the adhesion of Jeko-1 to the stromal occurred despite the combined use of Abs, suggesting that the efforts to mitigate migration of MCLs should be attempted as much as possible. Our results provide a basis for a future development of therapeutic strategies targeting both CXCR4 and VLA-4, such as Ab combinations or bispecific antibodies, to improve treatment outcomes of MCL with grave prognosis.

• Journal of Microbiology and Biotechnology
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• v.23 no.1
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• pp.118-124
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• 2013

Vibrio parahaemolyticus in uncooked seafood causes acute gastroenteritis. The microorganism has two sets of type III secretion systems and two hemolysins. When it injects its effector proteins into a host cell via type III secretion system 1, one of the type III secretion systems induces secretion of interleukin (IL)-8, a proinflammatory chemokine, through the phosphorylation of ERK 1/2 and p38 MAPK. Although probiotics have beneficial effects on hosts and can help control some infectious diseases, there is little research on the efficacy of probiotics in V. parahaemolyticus infection. Here we pretreated V. parahaemolyticus-infected human intestinal epithelial cells with heat-killed Lactobacillus brevis KB290, a probiotic isolated from fermented vegetables (traditional Japanese pickles) and utilized as an ingredient of beverages and supplementary foods, and demonstrated its efficacy in enhancing IL-8 secretion from V. parahaemolyticus-infected cells. Among the three heat-killed lactic acid bacterial strains we tested, L. brevis KB290 induced the highest level of IL-8 secretions in the infected cells. Relative to control cells (Caco-2 cells pretreated with PBS), V. parahaemolyticus-infected Caco-2 cells pretreated with heat-killed L. brevis KB290 secreted IL-8 earlier, although concentrations were similar 450min after infection. Heat-killed L. brevis KB290 pretreatment also induced earlier ERK 1/2 phosphorylation, greater p38 MAPK phosphorylation, and enhanced IL-8 mRNA expression. Heat-killed L. brevis KB290 accelerated IL-8 secretion, a host cell immune response, in V. parahaemolyticus-infected cells. We consider this to be beneficial because IL-8 plays an important defensive role against infection, and would contribute to the repair of injured epithelial cells.

• Molecules and Cells
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• v.39 no.7
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• pp.536-542
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• 2016

Interleukin-17A is a member of the IL-17 family, and is known as CTLA8 in the mouse. It is produced by T lymphocytes and NK cells and has proinflammatory roles, inducing cytokine and chemokine production. However, its role in tumor biology remains controversial. We investigated the effects of locally produced IL-17A by transferring the gene encoding it into CT26 colon cancer cells, either in a secretory or a membrane-bound form. Expression of the membrane-bound form on CT26 cells dramatically enhanced their proliferation in vitro. The enhanced growth was shown to be due to an increased rate of cell cycle progression: after synchronizing cells by adding and withdrawing colcemid, the rate of cell cycle progression in the cells expressing the membrane-bound form of IL-17A was much faster than that of the control cells. Both secretory and membrane-bound IL-17A induced the expression of Sca-1 in the cancer cells. When tumor clones were grafted into syngeneic BALB/c mice, the tumor clones expressing the membrane-bound form IL-17A grew rapidly; those expressing the secretory form also grew faster than the wild type CT26 cells, but slower than the clones expressing the membrane-bound form. These results indicate that IL-17A promotes tumorigenicity by enhancing cell cycle progression. This finding should be considered in treating tumors and immune-related diseases.