• Title/Summary/Keyword: immunostimulation

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Extracellular Signal-Regulated Kinase (ERK1/2) Regulate Glucose Deprivation-Induced Cell Death in Immunostimulated Astrocytes

  • Yoo, Byoung-Kwon;Park, Ji-Woong;Yoon, Seo-Young;Jeon, Mi-Jin;Park, Gyu-Hwan;Chun, Hyun-Joo;Ko, Kwang-Ho
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.83-83
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    • 2003
  • In our previous study, glucose deprivation was reported to induce the potentiated death and ATP loss in immunostimulated astroglia. And this vulnerability to glucose deprivation was due to overproduction of nitric oxide (NO) and hydrogen peroxide (H$_2$O$_2$). In the present study, the role of extracellular signal-regulated kinase 1/2 (ERK1/2) in the glucose deprivation-induced death of immunostimulated astroglia was examined. We showed that immunostimulation with LPS+IFN-ν activated the ERKl/2 signal pathway and produced a large amount of NO and H$_2$O$_2$. Generation of NO and H$_2$O$_2$ in immunostimulated astroglia was mediated via ERK1/2 signal pathways, since addition of the ERK kinase (MEKl) inhibitor PD98059 reduced NO and H$_2$O$_2$production. ERK1/2 activation-mediated NO and H$_2$O$_2$ production is due to an activation of iNOS and NADPH oxidase, respectively. Finally, we found that glucose deprivation caused ATP depletion and the augmented death in immunostimulated astroglia, which was also prevented by PD98059 treatment. These results demonstrate that the ERK1/2 signal pathways play an important role in glucose deprivation induced the death in immunostimulated astroglia by regulating the generation of NO and H$_2$O$_2$.

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The Effect of Kuwonsimsin-hwan on Immunosuppression Induced by Methotrexate in Rat (구원심신환(究原心腎丸)이 methotrexate로 유발된 흰쥐의 면역기능저하(免疫機能低下)에 미치는 영향(影響))

  • Choi, Soon-Ho;Kang, Seok-Bong;Choi, Sun-Mi;Lee, Yeon-Kyeong
    • The Journal of Korean Medicine
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    • v.28 no.2 s.70
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    • pp.126-136
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    • 2007
  • Objectives : In the present study, the effect of Kuwonsimsin-hwan (KSS) was tested in methotrexate (MTX)-induced immunosuppressed SD rats. Methods : Methotrexate was fed to white rats once a day for 4 days. After the immune responses of the rats deteriorated, dried extracts of Kuwonsimsin-hwan mixed in water was fed to the rats once a day for 14 days. We then measured the number of lymphocytes in peripheral blood and the percentage of B-cells, T-cells, CD3+CD4+T-cells, CD3+CD8+ T-cells and IL-2 productivity sampled from spleen and peripheral region. Results : (1) The number of lymphocytes and the percentage of T-cells and CD3+CD4+ T-cellsin peripheral blood increased significantly in the KSS group as compared with the control group. (2) The percentage of B-cells, CD3+CD8+ T-cells, and CD4+/CD8+ T-cells in peripheral blood were not different statistically. (3) The percentage of T-cells in spleen and IL-2 productivity of spleen cells increased significantly in the KSS group as compared with the control group. (4) The percentage of CD3+CD4+ T-cells in spleen increased in KSS the group as compared with the control group but without statistical significance. (5) The percentage of B-cells, CD3+CD8+ T-cells, and CD4+/CD8+ T-cells in spleen were not different statistically. Conclusion : It is concluded that Kuwonsimsin-hwan has immunostimulating effect on MTX-induced immunosuppressed SD rats.

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Bacterial strains isolated from Jeotgal (salted seafood) induce maturation and cytokine production in mouse bone marrow-derived dendritic cells (마우스 골수 유래 수지상세포의 성숙과 사이토카인 생산에 대한 젓갈 분리균의 효과 연구)

  • Moon, Sun-Young;Park, Eun-Jin;Joo, Hong-Gu
    • Korean Journal of Veterinary Research
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    • v.54 no.3
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    • pp.139-146
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    • 2014
  • Jeotgal (salted seafood) has been one of major fermented foods in Korea for long time. Although there are many studies about Jeotgal in various aspects of food, its immunological importance on hosts has not been elucidated yet. In this study, we investigated if several bacteria isolated from Jeotgal may modulate the function of dendritic cells (DCs), powerful antigen-presenting cells equipped with special immunological capabilities. 4 Jeotgal bacteria were selected as representatives and used for experiments. To treat viable DCs, those bacteria were killed at $60^{\circ}C$ for 30 min. The viability of DCs treated with Jeotgal bacteria was verified and two isolates significantly induced high production of interleukin-12, a representative cell-mediated cytokine of DCs. Surface activation and maturation markers (MHC class II, CD40, CD86) of DCs were analyzed by flow cytometer. In addition, the treated DCs showed significantly high lymphocyte stimulatory capability compared to control DCs based on allogeneic mixed lymphocyte reactions. These observations suggest that Jeotgal isolates can function as immunostimulating bacteria in hosts, like Lactobacillus. Taken together, these experimental evidences may broaden the use of Jeotgal isolates in immunological fields in addition to as a fermented food.

RAW264.7 Cell Activating Glucomannans Extracted from Rhizome of Polygonatum sibiricum

  • Yelithao, Khamphone;Surayot, Utoomporn;Lee, Ju Hun;You, SangGuan
    • Preventive Nutrition and Food Science
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    • v.21 no.3
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    • pp.245-254
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    • 2016
  • Water-soluble polysaccharides isolated from the rhizome of Polygonatum sibiricum and fractionated using ionexchange chromatography were investigated to determine their structure and immunostimulating activity. Crude and fractions ($F_1$ and $F_2$) consisted of carbohydrates (85.1~88.3%) with proteins (4.51~11.9%) and uronic acid (1.79~7.47%), and included different levels of mannose (62.3~76.3%), glucose (15.2~20.3%), galactose (4.35~15.3%), and arabinose (4.00~7.65%). The crude contained two peaks with molecular weights (Mw) of $151{\times}10^3$ and $31.8{\times}10^3$, but $F_1$ and $F_2$ exhibited one major peak with Mw of $103{\times}10^3$ and $628{\times}10^3$, respectively. Little immunostimulatory activity was observed by the crude; however, $F_1$ and $F_2$ significantly activated RAW264.7 cells to release nitric oxide and various cytokines, suggesting they were potent immunostimulators. The backbone of the most immunostimulating fraction ($F_1$) was ($1{\rightarrow}4$)-manno- and ($1{\rightarrow}4$)-gluco-pyranosyl residues with galactose and glucose attached to O-6 of manno-pyranoside.

Enzyme Hydrolysates of Ginseng Marc Polysaccharides Promote the Phagocytic Activity of Macrophages Via Activation of TLR2 and Mer Tyrosine Kinase

  • Seo, Jeong Yeon;Choi, Ji Won;Lee, Jae Yeon;Park, Young Shik;Park, Yong Il
    • Journal of Microbiology and Biotechnology
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    • v.28 no.6
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    • pp.860-873
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    • 2018
  • Although ginseng marc is a by-product obtained during manufacturing of various commercial ginseng products and has been routinely discarded as a waste, it still contains considerable amounts of potential bioactive compounds, including saponins and polysaccharides. Previously, we reported that ginseng oligosaccharides derived from ginseng marc polysaccharides by enzymatic hydrolysis exert immunostimulatory activities in macrophages and these activated macrophages are in turn able to inhibit the growth of skin melanoma cells by inducing apoptosis. In the present study, a more detailed investigation of the immunostimulatory activity and underlying action mechanisms of an enzymatic hydrolysate (GEH) containing these oligosaccharides derived from ginseng marc polysaccharides was performed. The levels of proinflammatory cytokines and anti-inflammatory cytokines were measured in GEH-stimulated RAW264.7 macrophages using RT-PCR analysis and ELISA. The expression levels of Toll-like receptor 2 (TLR2) and TLR4, Dectin-1, and MerTK were measured by RT-PCR analysis or western blot analysis, and the phagocytic activities of GEH-challenged bone marrow-derived macrophages toward apoptotic Jurkat cells were assayed using fluorescence microscopy. GEH induced the production of both proinflammatory cytokines $TNF-{\alpha}$ and IL-6, and anti-inflammatory cytokine IL-10 in RAW 264.7 cells. The expression of the TLR2 and MerTK mRNAs was increased upon GEH treatment. Phagocytosis of apoptotic Jurkat cells was enhanced in GEH-treated macrophages. Based on the results, this enzymatic hydrolysate (GEH) containing oligosaccharides exerts immunostimulatory effects by maintaining the balance between M1 and M2 cytokines, facilitating macrophage activation and contributing to the efficient phagocytosis of apoptotic cells. Therefore, the GEH could be developed as value-added, health-beneficial food materials with immunostimulatory effects.

Biotransformation of Intestinal Bacterial Metabolites of Ginseng Saponin to Biologically Active Fatty-acid Conjugates

  • Hasegawa Hideo;Saiki Ikuo
    • Proceedings of the Ginseng society Conference
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    • 2002.10a
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    • pp.317-334
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    • 2002
  • Ginsenosides are metabolized (deglycosylated) by intestinal bacteria to active forms after oral administration. 20(S)-Protopanaxadiol $20-O-{\beta}-D-glucopyranoside$ (M1) and 20(S)-protopanaxatriol (M4) are the main intestinal bacterial metabolites (IBMs) of protopanaxadiol- and protopanaxatriol-type glycosides. M1 was selectively accumulated into the liver soon after its intravenous (i.v.) administration to mice, and mostly excreted as bile; however, some M1 was transformed to fatty acid ester (EMl) in the liver. EM1 was isolated from rats in a recovery dose of approximately $24mol\%.$ Structural analysis indicated that EM1 comprised a family of fatty acid mono-esters of M1. Because EM1 was not excreted as bile as Ml was, it was accumulated in the liver longer than M1. The in vitro cytotoxicity of M1 was attenuated by fatty acid esterification, implying that esterification is a detoxification reaction. However, esterified M1 (EM1) inhibited the growth of B16 melanoma more than Ml in vivo. The in vivo antitumor activity paralleled with the pharmacokinetic behavior. In the case of M4, orally administered M4 was absorbed from the small intestine into the mesenteric lymphatics followed by the rapid esterification of M4 with fatty acids and its spreading to other organs in the body and excretion as bile. The administration of M4 prior to tumor injection abrogated the enhanced lung metastasis in the mice pretreated with 2-chloroadenosine more effectively than in those pretreated with anti-asialo GMl. Both EM1 and EM4 did not directly affect tumor growth in vitro, whereas EM1 promoted tumor cell lysis by lymphocytes, particularly non-adherent splenocytes, and EM4 stimulated splenic NK cells to become cytotoxic to tumor cells. Thus, the esterification of IBM with fatty acids potentiated the antitumor activity of parental IBM through delay of the clearance and through immunostimulation. These results suggest that the fatty acid conjugates of IBMs may be the real active principles of ginsenosides in the body.

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Immunostimulatory effects of dairy probiotic strains Bifidobacterium animalis ssp. lactis HY8002 and Lactobacillus plantarum HY7717

  • Ju-Yeon, Kim;Joo Yun, Kim;Hyeonji, Kim;Eun Chae, Moon;Keon, Heo;Jae-Jung, Shim;Jung-Lyoul, Lee
    • Journal of Animal Science and Technology
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    • v.64 no.6
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    • pp.1117-1131
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    • 2022
  • Previous studies reported that Bifidobacterium animalis ssp. lactis HY8002 (HY8002) improved intestinal integrity and had immunomodulatory effects. Lactobacillus plantarum HY7717 (HY7717) was screened in vitro from among 21 other lactic acid bacteria (LAB) and demonstrated nitric oxide (NO) production. The aims of this study were to investigate the individual and combined ex vivo and in vivo effects of LAB strains HY8002 and HY7717 at immunostimulating mice that have been challenged with an immunosuppressant drug. The combination of HY8002 and HY7717 increased the secretion of cytokines such as interferon (IFN)-γ, interleukin (IL)-12, and tumor necrosis factor (TNF)-α in splenocytes. In a cyclophosphamide (CTX)-induced immunosuppression model, administration of the foregoing LAB combination improved the splenic and hematological indices, activated natural killer (NK) cells, and up-regulated plasma immunoglobulins and cytokines. Moreover, this combination treatment increased Toll-like receptor 2 (TLR2) expression. The ability of the combination treatment to upregulate IFN-γ and TNF-α in the splenocytes was inhibited by anti-TLR2 antibody. Hence, the immune responses stimulated by the combination of HY8002 and HY7717 are associated with TLR2 activation. The preceding findings suggest that the combination of the HY8002 and HY7717 LAB strains could prove to be a beneficial and efficacious immunostimulant probiotic supplement. The combination of the two probiotic strains will be applied on the dairy foods including yogurt and cheese.

Induction of Autophagy by Rosa acicularis Leaves Extracts in RAW264.7 Cells (인가목(Rosa acicularis Lindl.) 잎 추출물의 대식세포에서 자가포식 유도활성)

  • Jeong Won Choi;Jin Boo Jeong
    • Korean Journal of Plant Resources
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    • v.36 no.4
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    • pp.257-263
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    • 2023
  • Autophagy contributes to enhancing the immune system (innate and adaptive immune system) against foreign pathogens. Autophagy of macrophages is used as a major indicator for developing vaccine adjuvants to increase the adaptive immune response. In this study, water extracts from Rosa acicularis leaves (RAL) increased the production of immunostimulatory mediators and phagocytic activity in RAW264.7 cells. RAL increased p62/SQSTM1 expression. Inhibition of TLR4, JNK, and PI3K/AKT blocked RAL-mediated increase of p62/SQSTM1. RAL activated JNK and PI3K/AKT signaling. RAL-mediated activations of JNK and PI3K/AKT signaling were reversed by TLR4 inhibition. Taken together, it is believed that RAL-mediated autophagy may be dependent on activating via TLR4-dependent activation of JNK and PI3K/AKT signaling in macrophages.

Effect of Jehotang Extract on the Growth of Intestinal Bacteria and Immunostimulation (제호탕의 장내 세균 및 면역 활성에 미치는 연구)

  • Ji, Myoung-Soon;Park, Min-Jung;Lee, Mi-Young;Kim, Jong-Goon;Ko, Byoung-Seob
    • Korean Journal of Food Science and Technology
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    • v.38 no.1
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    • pp.104-108
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    • 2006
  • Water extracts of Jehotang were evaluated for their growth-promoting effects on Bifidobacterium longum, Lactobacillus sp., L. acidophilus, and Clostridium perfringens. Addition of Jehotang water extract to modified EG media at 0.1 mg/mL increased growths of B. longum, Lactobacillus sp., and L. acidophilus, with 1.8-fold increase in growth of L. acidophilus compared to that of control. Studies on these strains by agar diffusion method showed Lactobacillus sp. and L. acidophilus were activated by addition of Jehotang extract at 10 mg/disc. Proliferation responses of mice splenocytes and Peyer's patch cells to ConA by LPS-stimulation at 500 mg/kg B.W./day Jehotang extract were investigated in vitro. Upon treatment of 1 mg/mL Jehotang water extract to mice, proliferations of splenocytes and Peyer's patch cells increased 1.4- and 1.6-fold compared to control, respectively. In mice administered Jehotang extract, production of intestinal secretory IgA (sIgA) increased 2.4-fold compared to control. These results indicate water extract of Jehotang stimulated intestinal immune system of mice. In mice treated with Jehotang extract, production of lymphocytes was 4% lower, whereas those of granulocytes and platelets were 4% and slightly higher than control, respectively.

Effects of Dietary Supplementation of Illite on Humoral Immunity against Salmonella typhimurium Flagella Antigen in Laying Hens (산란계에 Illite 급여가 Salmonella typhimurium 편모항원에 대한 체액성 면역 반응에 미치는 영향)

  • Lee, S.R.;Lee, S.;Chang, K.T.;Kim, J.W.
    • Korean Journal of Poultry Science
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    • v.36 no.3
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    • pp.201-206
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    • 2009
  • This study was carried out to investigate dietary effects of illite on humoral immune response against Salmonella typhimurium flagella in Hyline Brown laying hens. Total of twenty eight 36-week-old hens were divided into two groups; The first was fed commercial diet as control and the other was fed diet containing 2 % illite. Each group was divided into 2 sub-groups and then performed immunization of Salmonella flagella with different adjuvants which were Freund's adjuvant and croton oil. The rates of egg-production in all groups were normal range but no difference was found between illite-treated and untreated groups. The serum antibody titers of Freund's adjuvant-used subgroup in illite fed groups were significantly increased, especially from 6-to 9-week after $1^{st}$ immunization compared to those of control groups (p<0.05). And the antibody titers of croton oil-used subgroup in illite-fed groups were also significantly increased, especially at 4-, 6- and 7-week (p<0.05). The results demonstrated that the feeding illite stimulated the immune response against S. typhimurium flagella antigen in laying hens and suggest that the supplementation of illite to the poultry diets may support protective effects against bacterial infections such as Salmonellosis.