• IMMUNE NETWORK
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• v.7 no.4
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• pp.197-202
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• 2007

Background: Immunomodulators enhancing MHC-restricted antigen presentation would affect many cellular immune reactions mediated by T cells or T cell products. However, modulation of MHC-restricted antigen presentation has received little attention as a target for therapeutic immunoregulation. Here, we report that lectins isolated from mushroom Fomitella fraxinea enhance MHC-restricted exogenous antigen presentation in professional antigen presenting cells (APCs). Methods: Lectins, termed FFrL, were isolated from the carpophores of Fomitella fraxinea, and its effects on the class I and class II MHC-restricted presentation of exogenous ovalbumin (OVA) were examined in mouse dendritic cells (DCs) and mouse peritoneal macrophages. The effects of FFrL on the expression of total MHC molecules and the phagocytic activity were also examined in mouse DCs. Results: DCs cultured in the presence of FFrL overnight exhibited enhanced capacity in presenting exogenous OVA in association with class I and class II MHC molecules. FFrL increased slightly the total expression levels of both class I (H-$2K^b$) and class II (I-$A^b$) MHC molecules and the phagocytic activity of DCs. Antigen presentation-enhancing activity of FFrL was also observed in macrophages isolated from mouse peritoneum. Conclusion: Lectins isolated from the carpophores of Fomitella fraxinea increase MHC-restricted exogenous antigen presentation by enhancing intracellular processing events of phagocytosed antigens.

• Journal of Microbiology and Biotechnology
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• v.26 no.10
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• pp.1668-1674
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• 2016

Red ginseng, a steamed and sun-dried ginseng, is a popular health-promoting food in Korea and other Asian countries. We introduced nanofertilizer technology using gold nanoparticles in an effort to develop red ginseng with an elevated level of ginsenosides, the main active compounds of ginseng. Shoots of 6-year-old ginseng plants were fertilized three times with colloidal gold nanoparticle sprays. Red ginseng extract was prepared from the main roots. The concentrations of gold and ginsenosides were measured following gold nanoparticle treatment. To evaluate the anti-inflammatory effects, mouse peritoneal macrophages of male BALB/c mouse were stimulated with lipopolysaccharide plus interferon-γ in the presence of extracts from red ginseng with or without gold nanoparticle treatment. The content of ginsenosides, such as Rg1, Re, Rf, and Rb1, increased in ginseng treated with gold nanofertilizer whereas the steaming process increased only the levels of Rd and Rg3. The levels of nitric oxide, inducible nitric oxide synthase, and interleukin-6, but not tumor necrosis factor-α, were more suppressed in macrophages treated with extract from gold nanoparticle-treated red ginseng. Our results show that the use of a colloidal gold nanoparticle fertilizer improved the synthesis of ginsenosides in ginseng and enhanced the anti-inflammatory effects of red ginseng. Further research is required to elucidate the causal factors for the gold-induced change in ginsenoside synthesis and to determine the in vivo effect of gold nanoparticle-treated ginseng.

• Natural Product Sciences
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• v.20 no.4
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• pp.227-231
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• 2014

Cimicifuga heracleifolia extract (CHE) was investigated for its effects on the release of nitric oxide (NO) and at the level of inducible nitric oxide synthase (iNOS) gene expression in mouse macrophages. We found that C. heracleifolia elicited a dose-dependent increase in NO production and the level of iNOS mRNA. Since, iNOS transcription has been shown to be under the control of the transcription factor $NF-{\kappa}B$, the effects of CHE on $NF-{\kappa}B$ activation were examined. Transient expression assays with $NF-{\kappa}B$ binding sites linked to the luciferase gene revealed that the increased level of iNOS mRNA, induced by CHE, was mediated by the $NF-{\kappa}B$ transcription factor complex. By using DNA fragments containing the $NF-{\kappa}B$ binding sequence, CHE was shown to activate the protein/DNA binding of $NF-{\kappa}B$ to its cognate site, as measured by electrophoretic mobility shift assay. These results demonstrate that C. heracleifolia stimulates NO production and is able to up-regulate iNOS expression through $NF-{\kappa}B$ transactivation.

• Parasites, Hosts and Diseases
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• v.39 no.1
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• pp.67-76
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• 2001

This experiment was focused on the characterization of anti- Toxoplasma monoclonal antibodies (mAbs) and the effect of mAbs on the parasite invasion of mouse peritoneal macrophages. Twenty eight mAbs including M110, M556, R7A6 and M62l were characterized by Ab titer, immunoglobulin isotyping and western blot pattern. Antibody titer (optical density) of 4 mAbs. Ml 10. M556. R7A6 and M62l. were 0.53,0.67, 0.45 and 0.39 (normal mouse serum; 0.19) with the same IgGl isotypes shown by Enzyme-linked immunosorbent assay (ELISA). Western blot analysis showed that Ml 10. M556. R7A6 and M62l reacted with the 33 kDa (p30),31 kDa (p28),43 kDa and 36 kDa protein. Immuno-gold labelling of mAbs M110, M556, R7A6 and M621 reacted with the surface membrane, dense granules and parasitophorous vacuolar membrane (PVM) , rhoptries and cytoplasm of tachyzoite, respectively. For in vitro assay, preincubation of tachyzoties with four mAbs, Ml 10, M556, R7A6 and M62l resulted in the decrease of the number of infected macrophages (p < 0.05) and the suppression of parasite multiplication at 18 h post-infection. Four monoclonal antibodies including Ml 10 (SAGI) were found to have an important role in the inhibition of macrophage invasion and T. gondii multiplication in vitro, and these mAbs may be suitable for vaccine candidates, diagnostic kit and for chemotherapy.

• Korean Journal of Food Science and Technology
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• v.34 no.3
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• pp.510-517
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• 2002

Effects of wheat arabinoxylan on mouse spleen lymphocytes and peritoneal macrophages were examined in vitro. Among three wheat arabinoxylans (A1: low MW, A2: medium MW, A3: high MW), A3$(50{\sim}100\;{\mu}g/mL)$ increased the viability of spleen lymphocytes up to $114{\sim}125%$ of the control. A1 and A3 $(20\;{\mu}g/mL)$ increased the viability of lipopolysaccharide-treated lymphocytes synergistically. Viability of murine peritoneal macrophages treated with wheat arabinoxylans $(10{\sim}100{\mu}g/mL)$ was increased up to $135{\sim}175%$ of the control. The cytotoxic activity of macrophages against murine lymphocytic leukemic cell increased in the presence of wheat arabinoxylan. Phagocytic index of macrophages treated with wheat arabinozylans $(20\;{\mu}g/mL)$ significantly increased $197{\sim}232%$ compared with the control, and lysosomal phosphatase and myeloperoxidase activities also increased significantly (p<0.05). Treatment of wheat arabinoxylans tended to decrease nitrite production, but significantly stimulated $H_2O_2\;and\;O_2$ productions of macrophages (p<0.05). These results indicate that the immunostimulating effect of wheat arabinoxylan may be closely related with lysosomal enzyme activity and reactive oxygen intermediate production of macrophages.

• Korean Journal of Veterinary Research
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• v.34 no.4
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• pp.769-779
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• 1994

The root of Bupleurum falcatum L.(BF) has been widely used in oriental medicine as a major camponent in many prescriptions for chronic hepatitis, renal disease, tuberculosis and some other infectious diseases. Many attempts have done to investigate the therapeutic effects of these principles. However, any kinds of screenig on immune regulatory- and antitumor- effects of BF has not been reported. The present study, therefore, was undertaken to investigate the BF-effects on cellular- and humoral-immune responses, phagocytic activities of macrophages, lymphokine- and Immunoglobulin(Ig)-production of lymphocytes, tumorigenesis of implanted sarcoma 180 cells and B16 melanoma cells, and proliferations of some tumor cell lines(Fsa II, 3LL and EL4). BF increased phagocytic activities of mouse peritoneal macrophages in a dose- and time-dependent fashion. Arthus reaction and antibody responses to SRBC were slightly enhanced but delayed hypersensitivity was depresed when BF was injected before- and after-SRBC sensitization. BF inhibited the proliferative responses of human tonsillar lymphocytes to PHA- and Con A-stimulation but slightly augmented the response of these cells to Staphylococcus aureus Cowan 1(SAC)-activation. Ig secretion of human mononuclear cells activated with SAC was slightly increased by BF. BF significantly augmented the SAC-induced IL 6 production of human mononuclear cells but not influenced Con Ainduced IL 2 secretion. NK cell activities of mouse splenocytes were somewhat increased when BF was pretreated and this responses were due to the increment of binding affinities of effector cells to target cells and of lytic activities of effector cells against target cells. In vitro BF significantly inhibited the proliferations of cancer cells such as Fsa II, 3LL and EL4 strains. BF decreased not only the frequency of tumor induction but also the tumor size per sarcoma 180 or B16 cell-implanted mouse. Taken together, these results indicate that BF is one of the potential immunomodulator, and suggest its possibility to be used as a desirable antitumor agent.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.28 no.4
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• pp.92-110
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• 2015

Objectives : The water extract of Bowon-tang composited with thePanax, AstragalusandGlycyrrhiza Radixhas been traditionally used for treatment of a sickly child and smallpox in oriental medicine. However, little is known about the regulatory effects of Bowon-tang on the production, expression and activity of immune mediators [nitric oxide, prostaglandin E2, inducible nitric oxide synthetase, cyclooxygenase-2], the macrophage activation factor production, the proliferation, subset expression, the killing activity, and the capping in immune cells.Methods : In this study, we investigated the effects of water extracts from Bowon-tang,Panax, AstragalusorGRin mouse immune cells or human Jurkat T cells. Each extract (25-200 ㎍/㎖)perse had no cytotoxic effect in unstimulated macrophages, but concentration-dependently regulated NO and PGE₂production, iNOS expression, and COX-2 activity in mouse peritoneal macrophages with MAF stimulation. These regulatory effects were synergistically increased by their combination (Bowon-tang).Results : The extract of Bowon-tang concentration-dependently regulated T cell proliferation, CD4⁺and CD8⁺expression, and NK killing activity in mouse splenocytes and capping in Jurkat T cells.Conclusions : These results suggest that the water extract of Bowon-tang composited with thePanax, AstragalusandGRmay be useful for therapeutic drugs against a sickly constitution and immune diseases, probably by regulating the production of immune mediators.

• KSBB Journal
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• v.17 no.6
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• pp.520-524
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• 2002

The present study was designed to investigate the effects of Stachys Sieboldii MIQ as a new natural antitumor agent or immunomodulator. To obtain the above objectives, Stachys sieboldii MIQ was extracted with ethanol. Stachys sieboldii MIQ accelerated mouse spleen cell growth, but inhibited FM3A/S°-cell growth. However, no significant difference was found for CD4+ / CD8+ cells. The growth rates of CD4+ and CD8+ T cells were accelerated more than those normal mouse group. Stachys sieboldii MIQ fed mice showed a significant enhancement of IL-2 receptor expression, increased numbers of CD4+ T cells, and CD8+ T cells. Stachys sieboldii MIQ also stimulated the production of NO by peritoneal macrophages and the production of NO by and the growth of mouse spleen cells. On the other hand, lung localization of Bl6Fl0 melanoma cells was inhibited by ethanol extract of Stachys sieboldii MIQ. These results show that Stachys sieboldii MIQ is a useful new functional antitumor agent or immunomodulator.

• BMB Reports
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• v.33 no.6
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• pp.463-468
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• 2000

Anthrax lethal toxin, which consists of two separate protein, protective antigen (83 KDa) and lethal factor (85 KDa) is responsible for major symptoms and death from systemic infection of Bacillus anthracis. High concentrations of this toxin are cytolytic to macrophages, whereas sublytic concentrations of lethal toxin induce these cells to produce interleukin $1{\beta}$ ($IL-1{\beta}$). It is proposed that melatonin and dehydroepiandrosterone (DHEA) may play an important role in modifying immune dysfunction. In this study, we investigated whether or not melatonin and DHEA could prevent $IL-1{\beta}$ production that is induced by anthrax lethal toxin in mouse peritoneal macrophages. Treatment of melatonin or DHEA alone, as well as together, prevented the production of $IL-1{\beta}$ caused by anthrax lethal toxin. We found that melatonin at a concentration of $10^{-6}-10^{-7}$ M inhibits $IL-1{\beta}$ production induced by anthrax lethal toxin. As expect, treatment of DHEA at a concentration $10^{-6}-10^{-7}$ M also suppressed production of $IL-1{\beta}$ by lethal toxin stimulated macrophages. The results of these studies suggest that melatonin and DHEA, immunomodulators, may have an important role in reducing the increase of cytokine production in anthrax lethal toxin-treated macrophages.

• Journal of Microbiology and Biotechnology
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• v.18 no.6
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• pp.1170-1178
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• 2008

The cyclopentenone prostaglandins (cyPGs) prostaglandin $A_1$ ($PGA_1$) and 15-deoxy-${\Delta}^{12,14}$-prostaglandin $J_2$ (15d-$PGJ_2$) have been reported to exhibit antiinflammatory activity in activated monocytes/macrophages. However, the effects of these two cyPGs on the expression of cytokine genes may differ. In this study, we investigated the mechanism of action of $PGA_1$ in lipopolysaccharide (LPS)-induced expression of inter leu kin (IL)-10 mRNA in mouse peritoneal macrophages. 15d-$PGJ_2$ inhibited expression of LPS-induced IL-10, whereas $PGA_1$ increased LPS-induced IL-10 expression. This synergistic effect of $PGA_1$ on LPS-induced IL-10 expression reached a maximum as early as 2 h after simultaneous $PGA_1$ and LPS treatment ($PGA_1$/LPS), and did not require new protein synthesis. The synergistic effect of $PGA_1$ was inhibited by GW9662, a specific peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$ antagonist, and Bay-11-7082, a NF-${\kappa}B$ inhibitor. The extracellular signal-regulated kinases (ERK) inhibitor PD98059 increased the expression of $PGA_1$/LPS-induced IL-10 mRNA, rather than inhibiting the IL-10 expression. Moreover, $PGA_1$ inhibited LPS-induced ERK phosphorylation. The synergistic effect of $PGA_1$ on LPS-induced IL-10 mRNA and protein production was inhibited by p38 inhibitor PD169316, and $PGA_1$ increased LPS-induced p38 phosphorylation. In the case of stress-activated protein kinase/c-Jun $NH_2$-terminal kinase (SAPK/JNK), the SAPK/JNK inhibitor SP600125 did not inhibit IL-10 mRNA synthesis but inhibited the production of IL-10 protein remarkably. These results suggest that the synergistic effect of $PGA_1$ on LPS-induced IL-10 expression is NF-${\kappa}B$-dependent and mediated by mitogen-activated protein (MAP) kinases, p38, and SAPK/JNK signaling pathways, and also associated with the $PPAR{\gamma}$ pathway. Our data may provide more insight into the diverse mechanisms of $PGA_1$ effects on the expression of cytokine genes.