• Biomedical Science Letters
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• v.29 no.4
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• pp.211-219
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• 2023

Caffeic acid phenethyl ester (CAPE) is an active component of propolis obtained from honeybee hives. CAPE possesses anti-mitogenic, anti-carcinogenic, anti-inflammatory, and immunomodulatory activities in diverse systems, which know as displays antioxidant activity and inhibits lipoxygenase activities, protein tyrosine kinase, and nuclear factor kappa B (NF-κB) activation. This study aimed to investigate the effect of CAPE on lipopolysaccharide (LPS)-induced human neutrophil phagocytosis. Human neutrophils were cultured with various concentrations of CAPE (1, 10, and 100 µM) with or without LPS. The pro-inflammatory proteins (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6 and IL-8) levels were measured after 4 h incubation. To investigate the intracellular signaling pathway, we measured the levels of mitogen-activated protein kinases (MAPK), including phosphorylation of p38, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Next, to evaluate the potential phagocytosis, neutrophils were labeled with iron particles of superparamagnetic iron oxide nanoparticles (SPIONs, 40 nm) for 1 h in culture medium containing 5 mg/mL of iron. The labeling efficiency was determined by Prussian blue staining for intracellular iron and 3T-wighted magnetic resonance imaging. CAPE decreased the activation of intracellular signaling pathways, including ERK1/2 and c-Jun, and expression of pro-inflammatory cytokines, including TNF-α and IL-6, but had no effect on the signaling pathways of p38 and cytokine IL-8. Furthermore, images obtained after mannan-coated SPION treatment suggested that CAPE induced significantly higher signal intensities than the control or LPS group. Together, these results suggest that CAPE regulates LPS-mediated activation of human neutrophils to reduce phagocytosis.

• Korean Journal of Plant Resources
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• v.24 no.5
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• pp.557-563
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• 2011

Platycodon grandiflorum (Korean name, Doraji) has been widely used in traditional herbal medicine as an expectorant for pulmonary disease and a remedy for respiratory disorders in Asia. Here, we investigated the effects of BtOH extract saponin fraction of P. gradiflourm (PGS) on phagocytosis and anti-tumor activity with related cytokine productions in RAW264.7 macrophage cells. The results showed that PGS increased phagocytosis, anti-tumor activity, TNF-${\alpha}$ and nitric oxide (NO) production without direct tumor cell cytotoxicity. To further investigate whether NO is involved in anti-tumor and phagocytic activities of PGS, cells were co-treated with specific iNOS inhibitors, L-NIL (N6-(1-iminoethyl)-L-lysine, dihydrochloride), to block NO production. PGS decreased anti-tumor activity in L-NIL-treated cells, whereas phagocytic activity was not inhibited under the same conditions, indicating that the anti-tumor activity by PGS appears to be conducted by NO. These findings suggest that P. grandiflorum could be used a potential nutrition therapeutic agent for cancer patients.

• 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.

• Journal of Life Science
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• v.17 no.10
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• pp.1434-1440
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• 2007

We have investigated the effects of mushroom mycelium (Phellinus linteus, Coriolus versicolor) mixed cultural extract on the immune responses of olive flounder, Paralichthys olivaceus. The mixed culture extracts were evaluated for the growth, hematology, lysozyme activity, leukocyte phagocytic activity, and disease resistance against Vibrio anguillarum. In the effect of the growth, the body weight and length gain in the group, which fed with mushroom mycelium mixed cultural extract, were 52 g and 3.4 cm higher than that in the control, respectively. For the hematology, the administration of mushroom mycelium mixed cultural extract resulted in increase of glucose. However, there was no distinct differences in GOT (glutamic oxaloacetic transaminase), GPT (glutamlc pyruvic transamlnase), TG, TP, and LDH (lactate dehydronase) among each group. The activities of lysozyme were 80% higher in the experimental groups than in the control. The activities of leucocyte were 66% higher in the experimental groups than in the control. Although lysozyme activity and leucocyte activity showed somewhat decrease after 12 weeks, these activities were still higher than in the control. The cumulative mortality (%) after an artificial challenge with $7{\times}10^8\;CFU$ of Vibrio anguillarum per fish was 25% higher in the experimental groups than the control.

• Applied Microscopy
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• v.24 no.3
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• pp.10-22
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• 1994

To investigate the morphology of the synovial lining cells, synovitis was induced by carrageenin injection into the rat knee joint cavities. Synovial membranes were excised at 1, 3, 5, 7 and 14 days, and histologic, electron microscopic, histochemical (periodic acid Schiff: PAS, toluidine blue), and enzyme histochemical (acid phosphatase: ACP, nonspecific esterase: NSE and endogenous peroxidase) studies were performed. The results are as follows: Carrageenin induced synovial membrane hypertrophy with synovial cell proliferation and granuloma formation. The proliferated synovial lining cells and macrophages in the granulomatous lesion had round to oval nuclei and large, plump cytoplasm with many phagocytotic materials and vacuoles. Electron microscopically, these cells had small number of granular endoplasmic reticulum and many lysosomes, phagosomes and vaculoes. Mitotic figures were observed at early stage of experiment. PAS and toluidine blue stains showed strongly positive reaction in the cytoplasm of the proliferated lining cells and macrophages in granulomatous lesion. ACP and NSE activities were strong positive in the cytoplasm of the proliferated synovial lining cells and macrophages in the granulomatous lesion. But endogenous peroxidase stains were negative in all prolifeative lining cells and macrophages in granulomatous lesion. Conclusively, carrageenin-induced synovitis showed proliferation of synovial lining cells and granuloma formation in deep layer. The macrophages, which consisted of the lesions and have active phagocytic function, were speculated to proliferate by mitosis of superficial synovial A cells and histiocytes in the deep layer of the synovial membrane.

• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.293-298
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• 2009

Korean mistletoe lectin (KML) is the major component found in Viscum album var. (coloratum), displaying anti-cancer and immunostimulating activities. Even though it has been shown to boost host immune defense mechanisms, the regulatory roles of KML on the functional activation of macrophages have not been fully elucidated. In this study, regulatory mechanism of KML on macrophage-mediated immune responses was examined in terms of KML-mediated signaling event. KML clearly induced mRNA expression of tumor necrosis factor (TNF)-$\alpha$, the generation of reactive oxygen species (ROS) and phagocytic uptake in RAW264.7 cells. All of these events were strongly suppressed by U0126, whereas TNF-$\alpha$ mRNA was not diminished by SB203580 and SP600125, indicating ERK as a central enzyme managing KML-induced up-regulation of macrophage functions. Indeed, KML strongly induced the phosphorylation of ERK in a time-dependent manner without altering its total level. Therefore, these data suggest that ERK may be a major signaling enzyme with regulatory property toward various KML-mediated macrophage responses.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.7
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• pp.916-923
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• 2010

We report nutritional physiology and non-specific immune responses of vitamin E in parrot fish for the first time. This study aimed to investigate the essentiality and requirements in diets based on growth performances, non-specific immune responses and a challenge test against Vibrio angullarum. Six casein-gelatin based semi-purified diets were formulated to contain six graded levels of DL-${\alpha}$-tocopheryl acetate (${\alpha}$-TA) at 0, 25, 50, 75, 100 and 500 mg/kg diet (designated as E0, E25, E50, E75, E100 and E500, respectively) and fed to triplicate groups of juvenile parrot fish for 12 weeks. The analyzed dietary concentrations of vitamin E were 0, 38, 53, 87, 119 and 538 mg/kg diet for E0, E25, E50, E75, E100 and E500, respectively. At the end of the feeding trial, growth performance and feed utilization of fish fed the E25 were significantly higher compared to that of fish fed the other diets. Liver ${\alpha}$-tocopherol concentration was significantly increased with an increase in dietary ${\alpha}$-TA in a dose dependent manner. No apparent clinical signs of vitamin E deficiency and mortality were observed in fish fed the basal diet for 12 weeks. Among the immune responses assayed, phagocytic (NBT assay) and myeloperoxidase activities were significantly increased with increment of dietary ${\alpha}$-TA levels. During the challenge test with V. anguillarum, E75, E100, and E500 diets resulted in higher survivals than E0, E25 and E50 diets. The findings of this study suggest that parrot fish require exogenous vitamin E and the optimum dietary level could be approximately 38 mg ${\alpha}$-TA/kg diet for normal growth and physiology. Dietary ${\alpha}$-TA concentration over 500 mg/kg could be required to enhance the nonspecific immune responses and improve the resistance of juvenile parrot fish against V. anguillarum.

• Journal of Microbiology and Biotechnology
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• v.18 no.2
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• pp.355-364
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• 2008

Mushrooms are regarded as one of the well-known foods and biopharmaceutical materials with a great deal of interest. ${\beta}$-Glucan is the major component of mushrooms that displays various biological activities such as antidiabetic, anticancer, and antihyperlipidemic effects. In this study, we explored the molecular mechanism of its immunostimulatory potency in immune responses of macrophages, using exopolysaccharides prepared from liquid culture of Lentinus edodes. We found that fraction II (F-II), with large molecular weight protein polysaccharides, is able to strongly upregulate the phenotypic functions of macrophages such as phagocytic uptake, ROS/NO production, cytokine expression, and morphological changes. F-II triggered the nuclear translocation of NF-${\kappa}B$ and activated its upstream signaling cascades such as PI3K/Akt and MAPK pathways, as assessed by their phosphorylation levels. The function-blocking antibodies to dectin-1 and TLR-2, but not CR3, markedly suppressed F-II-mediated NO production. Therefore, our data suggest that mushroom-derived ${\beta}$-glucan may exert its immunostimulating potency via activation of multiple signaling pathways.

• IMMUNE NETWORK
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• v.10 no.4
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• pp.135-143
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• 2010

Background: Cordyceps militarys water extract (CME) has been reported to exert antitumor and immunomodulatory activities in vivo and in vitro. However, the therapeutic mechanism has not yet been elucidated. In this study, we examined the effects of CME on the antigen presenting function of antigen presenting cells (APCs). Methods: Dendritic cells (DCs) were cultured in the presence of CME, and then allowed to phagocytose microspheres containing ovalbumin (OVA). After washing and fixing the efficacy of OVA, peptide presentation by DCs were evaluated using CD8 and CD4 T cells. Also, we confirmed the protein levels of proinflammatory cytokines through western blot analysis. Results: CME enhanced both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the expression of both MHC class I and II molecules was enhanced, but there was no changes in the phagocytic activity of exogenous OVA. Furthermore, CME induced the protein levels of iNOS, COX-2, proinflammatory cytokines, and nuclear p65 in a concentration-dependent manner, as determined by western blot. Conclusion: These results provide an understanding of the mechanism of the immuno-enhancing activity of CME on the induction of MHC-restricted antigen presentation in relation to their actions on APCs.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.50 no.1
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• pp.8-14
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• 2017

A feeding trial was conducted to evaluate the effect of dietary supplementation with fermented soybean meal by Bacillus subtilis (BFSBM) on growth performance, feed utilization, innate immunity, water quality, and disease resistance of Litopenaeus vannamei. A basal fish meal-based diet was regarded as a control and two other diets were prepared by replacing 30% fish meal with either soybean meal (SBM) or BFSBM. Triplicate groups of shrimp ($0.80{\pm}0.010g$) were fed one of the experimental diets for 6 weeks. No differences were found in final body weight, feed conversion ratio, or survival among all dietary treatments after the feeding trial. Shrimp fed the BFSBM diet had significantly higher phagocytic and phenoloxidase activities than those of shrimp fed the SBM diet. Total ammonia concentrations in culture water during a zero water exchange test tended to decrease in tanks where BFSBM diet was provided. Disease resistance of shrimp to Vibrio harveyi tended to increase in the BFSBM group during 14 days of challenge compared to that in the control (CON) and SBM groups. These results show that dietary supplementation with BFSBM can enhance the innate immunity of Pacific white shrimp and replace at least 30% of dietary fish meal.