• IMMUNE NETWORK
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• v.6 no.1
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• pp.6-12
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• 2006

Background: The Hypothalamo-Pituitary-Adrenal (HPA) axis is an important regulator for the body's stress response. As a primary stress responsive system, HPA-axis secretes various neurotransmitters, hormones, and cytokines, which regulates the immune system. Natural killer (NK) cell which is plays an important role in the innate immune response, is specially decreased their numbers and loose cytolytic activity in response to stress. However, the effect of HPA-axis secreted proteins on NK cell activity has not been defined. Herein, we studied the effect of adrenal secreted adiponectin on NK cell cytotoxicity. Adiponectin which is well-known metabolic control protein, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. Methods: Signal sequence trap was used to find stress novel secretory protein from HP A-axis. Selected adiponectin was treated mouse mature primary NK cells and then examined the effect of adiponectin to NK cell cytotoxicity and cytokine expression level. Results: We found that adiponectin which is secreted from adrenal gland, suppress IL-2 induced NK cell cytotoxicity. And also investigated cytolytic cytokines are suppressed by adiponectin. Conclusion: These data suggest that adiponectin inhibites NK cell cytotoxicity via suppression of cytotoxicity related target gene.

• Food Science and Biotechnology
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• v.18 no.2
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• pp.323-329
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• 2009

The prescriptions (DB-1-DB-5) were prepared with the active herbal medicines, Acanthopanax senticosus, Glycyrrhiza uralensis, Polygonatum odoratum, and Cichorium intybus. The most active crude polysaccharide fraction (DB-2-3), which was isolated through the fractionation of hot-water extract from DB-2, was significantly reduced by periodate oxidation (52.7 and 63.7%) on intestinal immune system modulating and anticancer activity. When DB-2-3 was further fractionated by column chromatographies, DB-2-3IIc-2 showed the most potent activities. In addition, DB-2-3IIc stimulated the proliferation of bone marrow cells via Peyer's patch in dose-dependent pattern by oral administration. The metastasis of colon 26-M3.1 lung carcinoma had significantly inhibited in mice fed DB-2-3IIc at 1 mg/mouse (43.8%). DB-2-3IIc-2 mainly contained uronic acid (46.1%) and 42.5% of neutral sugar with a small amount of protein (7.6%), and component sugar analysis also showed that DB-2-3IIc-2 was composed Ara, Gal, and GalA (molar ratio; 0.50:0.63:1.00). It may be suggested that activities of DB-2-3IIc-2 are resulted from pectic polysaccharides containing a polygalacturonan moiety with side chain of neutral sugars, such as Ara and Gal.

• Preventive Nutrition and Food Science
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• v.19 no.1
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• pp.10-18
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• 2014

In this study, Woongjin fermented red ginseng extract (WFRG) was evaluated for its potential ability to act as an adjuvant for the immune response of mice. For the in vitro study, macrophages were treated with serial concentrations ($1{\mu}g/mL$, $10{\mu}g/mL$, and $100{\mu}g/mL$) of WFRG. For in vivo studies, mice were administered different concentrations (10 mg/kg/day, 100 mg/kg/day, and 200 mg/kg/day) of WFRG orally for 21 days. In vitro, the production of nitric oxide and TNF-${\alpha}$ by RAW 264.7 cells increased in a dose-dependent manner. In vivo, WFRG enhanced the proliferation of splenocytes induced by two mitogens (i.e., concanavalin A and lipopolysaccharide [LPS]) and increased LPS-induced production of TNF-${\alpha}$ and IL-6, but not IL-$1{\beta}$. In conclusion, WFRG has the potential to modulate immune function and should be further investigated as an immunostimulatory agent.

• The Korean Journal of Food And Nutrition
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• v.33 no.6
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• pp.732-736
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• 2020

Theobroma cacao L., a fruit of cacao trees, is a perennial plant, which belongs to Sterculiaceae, and is native to the Amazon in South Africa. It also has been known for its various biologically active effects, such as anti-oxidation, anti-cancer, and anti-bacterial. The spleen cell proliferations of mice were measured at 48 hours after treatment of Theobroma cacao L. water extracts in seven concentrations(0, 5, 10, 50, 100, 250, 500 and 1,000 ㎍/mL) an ELISA assay. The production of cytokine (IL-1β, TNF-α, IFN-γ), is secreted by macrophages stimulated with LPS, was detected by ELISA assay using the cytokine kit. From the results of in vitro study, both splenocytes and cytokine production activated by peritoneal macrophages have increased when water extracts were supplemented in the range between 250 and 500 ㎍/mL concentration. Notably, splenocytes production has a signigicant proliferation at 500 ㎍/mL concentration. The result from this research suggests that supplementation with Theobroma cacao L. water extracts may enhance the immune function by stimulating the splenocyte proliferation and improving the cytokine production activating macrophage in vitro.

• The Journal of Korean Obstetrics and Gynecology
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• v.32 no.4
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• pp.1-13
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• 2019

Objective: This study is aimed to investigate the anti-tumor metastasis by innate immunomodulating effects of crude polysaccharide isolated from Polygonati Rhizoma (CP-PR) on 4T1 breast cancer cells. Methods: CP-PR was isolated from Polygonati Rhizoma. Antimetastatic experiments were conducted in vivo mouse model by using 4T1 breast cancer cells. The cell viability of CP-PR was tested with normal spleen and 4T1 breast cancer cells. To observe the activation of macrophages with/without 4T1 breast cancer cells, production of tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), IL-10 and IL-12 were measured with enzyme-linked immunosorbent assay (ELISA), respectively. In addition, the lysis of YAC-1 cells and the production of granzymes were measured to observe the activation of natural killer (NK) cell. Results: Intravenous administration of CP-PR significantly inhibited metastasis of 4T1 breast cancer cells. In an in vitro cytotoxicity analysis, CP-PR affected the growth of normal spleen and 4T1 breast cancer cells above specific concentration. The production of $TNF-{\alpha}$, IL-6, IL-10 and IL-12 were significantly increased in macrophages with CP-PR. As compared with control, CP-PR showed significantly higher production of $TNF-{\alpha}$, IL-10 and IL-12 in macrophages co-cultured with 4T1 breast cancer cells. The lysis of YAC-1 cells and the production of granzymes were significantly up regulated by CP-PR. Conclusion: CP-PR appears to have considerable activity on the anti-metastasis by activation of innate immune system.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.7
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• pp.1092-1097
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• 2004

The objective of the current study was to determine the effects of the crude polysaccharide isolated from fruit body of Pleurotus eryngii on mouse splenocytes, B cells, and macrophages in vitro. The crude polysaccharides directly induced the proliferation of spleen cells in a dose-dependent manner and increased IL-6 and IFN-${\gamma}$ synthesis. The crude polysaccharides also increased the proliferation of B cells in a dose-dependent manner. The production of immunoglobulin Gl, G2a and IgG3 in the presence of the crude polysaccharides was increased progressively in the culture supernatant. When the crude polysaccharide were used in macrophage cell line (RA W264.7) stimulation, there were marked induction of NO synthesis in a dose-dependent manner and IL-6, TNF- r and GM-CSF synthesis. These results suggest that the crude polysaccharide isolated from fruit body of Pleurotus eryngii seem to act as a potent immunomodulator causing augmentation of immune cell activity, and thus could be used as a biological response modifier having possible therapeutic effects against immunological disorders, without any side effects.

• IMMUNE NETWORK
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• v.6 no.1
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• pp.13-19
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• 2006

Background: Granulocyte colony stimulating factor (G-CSF) is known as a cytokine central to the hematopoiesis of blood cells and to modulate their cellular functions. Besides granulocytes and their precursors, monocytes/macrophages and endothelial cells are direct target cells of G-CSF action. G-CSF influences immune cells in an anti inflammatory way. Methods: To evaluate whether G-CSF has a potential for preventing or ameliorating diseases characterized by mucosal inflammation, we used a mouse model with trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. To the mice model G-CSF was administrated daily by intraperitoneal injection. Macroscopic evaluation and immunohistochemical analysis of colonic tissues were performed. Results: Re combinant human G-CSF significantly inhibited LPS-induced TNF-${\alpha}$ mRNA expression in THP-1 cells. As for in vivo relevance, G-CSF dramatically reduced the weight loss of mice, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, G-CSF suppressed the expression of tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, and intercellular adhesion molecule-1 in TNBS colitis. Conclusion: Current results demonstrate that G-CSF may be an effective agent for the treatment of diseases characterized by mucosal inflammation.

• 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 Physiology & Pathology in Korean Medicine
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• v.24 no.4
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• pp.616-623
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• 2010

Three herbal formulas (Bangpungtongsung-san, Ohyaksungi-san, and Ojeok-san) for wind-cold and heat pain symptom were applied to investigate the immunological activities on antigen (Ag)-specific or Ag-non-specific immune responses in murine macrophage cell line (RAW 264.7) and ovalbumin (OVA)-immunized mice. This study was carried out in nitric oxide (NO) synthesis in RAW 264.7 cells and cellular proliferation in mouse splenocytes according to three herbal formulas. C57BL/6 mice were immunized intraperitonially with OVA/aluminium ($100\;{\mu}g/200\;{\mu}g$/mouse) on day 1, 8, and 15. Three herbal formulas were administrated to mice orally for 3 weeks from day 1. On day 22, OVA-, lipopolysaccharide (LPS)-, and concanavalin A (Con A)-stimulated splenocyte proliferation and antibodies (OVA-specific antibodies of the IgG, lgG1, and total IgM classes) in plasma were measured. Ohyaksungi-san increased NO synthesis in RAW 264.7 cells. Ojeok-san and Ohyaksungi-san significantly enhanced cellular proliferation by LPS and Con A in splenocytes from OVA-immunized mice (p<0.001). Three herbal formulas for wind-cold and heat pain symptom also significantly enhanced plasma OVA-specific IgG, IgG1, and total IgM levels compared with the OVA/Alum group. These results suggested that three herbal formulas for wind-cold and heat pain symptom could be used as stimulator of immune response.

• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1444-1452
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• 2019

The conventional prophylactic vaccines for human papillomavirus (HPV) efficiently prevent infection with high-risk HPV types, but they do not promote therapeutic effects against cervical cancer. Previously, we developed HPV16 E7-expressing Lactobacillus casei (L. casei-E7) as a therapeutic vaccine candidate for cervical cancer, which induces antitumor therapeutic effects in a TC-1 murine cancer model. To improve the therapeutic effect of L. casei-E7, we performed co-treatment with poly-gamma-glutamic acid (${\gamma}-PGA$), a safe and edible biomaterial naturally secreted by Bacillus subtilis. We investigated their synergistic effect to improve antitumor efficacy in a murine cancer model. The treatment with ${\gamma}-PGA$ did not show in vitro cytotoxicity against TC-1 tumor cells; however, an enhanced innate immune response including activation of dendritic cells was observed. Mice co-administered with ${\gamma}-PGA$ and L. casei-E7 showed significantly suppressed growth of TC-1 tumor cells and an increased survival rate in TC-1 mouse models compared to those of mice vaccinated with L. casei-E7 alone. The administration of ${\gamma}-PGA$ markedly enhanced the activation of natural killer (NK) cells but did not increase the E7-specific cytolytic activity of $CD8^+$ T lymphocytes in mice vaccinated with L. casei-E7. Overall, our results suggest that oral administration of ${\gamma}-PGA$ induces a synergistic antitumor effect in combination with L. casei-E7.