• Parasites, Hosts and Diseases
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• v.60 no.4
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• pp.255-259
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• 2022

Heliminthic paramyosin is a multifunctional protein that not only acts as a structural protein in muscle layers but as an immune-modulatory molecule interacting with the host immune system. Previously, we found that paramyosin from Clonorchis sinensis (CsPmy) is bound to human complement C9 protein (C9). To analyze the C9 binding region on CsPmy, overlapping recombinant fragments of CsPmy were produced and their binding activity to human C9 was investigated. The fragmental expression of CsPmy and C9 binding assays revealed that the C9 binding region was located at the C-terminus of CsPmy. Further analysis of the C-terminus of CsPmy to narrow the C9 binding region on CsPmy indicated that the region flanking ⁷³¹Leu-⁷⁸⁰Leu was a potent C9 binding region. The CsPmy fragments corresponding to the region effectively inhibited human C9 polymerization. These results provide a precise molecular basis for CsPmy as a potent immunomodulator to evade host immune defenses by inhibiting complement attack.

• Parasites, Hosts and Diseases
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• v.60 no.2
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• pp.117-126
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• 2022

Cystatin, a cysteine protease inhibitor found in many parasites, plays important roles in immune evasion. This study analyzed the molecular characteristics of a cystatin from Fasciola hepatica (FhCystatin) and expressed recombinant FhCystatin (rFhcystatin) to investigate the immune modulatory effects on lipopolysaccharide-induced proliferation, migration, cytokine secretion, nitric oxide (NO) production, and apoptosis in mouse macrophages. The FhCystatin gene encoded 116 amino acids and contained a conserved cystatin-like domain. rFhCystatin significantly inhibited the activity of cathepsin B. rFhCystatin bound to the surface of mouse RAW264.7 cells, significantly inhibited cell proliferation and promoted apoptosis. Moreover, rFhCystatin inhibited the expression of cellular nitric oxide, interleukin-6, and tumor necrosis factor-α, and promoted the expression of transforming growth factor-β and interleukin-10. These results showed that FhCystatin played an important role in regulating the activity of mouse macrophages. Our findings provide new insights into mechanisms underlying the immune evasion and contribute to the exploration of potential targets for the development of new drug to control F. hepatica infection.

• Korean Journal of Medicinal Crop Science
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• v.16 no.5
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• pp.349-355
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• 2008

Anticancer and immuno-modulatory activities of methanol extracts from different parts, bark, wood and leaf, of Cornus macrophylla Wall. were investigated in this study. All extracts at a concentration of 1.0mg/ml showed relativity low cytotoxicities on human normal kidney cell (HEK293) by approximately 25%. Bark extract of C. macrophylla showed the highest anticancer activity on human lung cancer cell line (A549) and human breast cancer cell line (MCF-7) by 57.4% and 58.7%, respectively, at a concentration of 1.0mg/ml. All extracts enhanced the growth of human B and T cells, showing 38.7% and 65.9% increase compared to control, respectively, by 5 days incubation with bark extract. The secretions of interleukin 6 (IL6) and tumor necrosis factor alpha (TNF-$\alpha$) from human B and T cells were significantly increased by extracts, especially bark extract. B or T cell medium, which contains cytokines (IL 6 and TNF-$\alpha$) secreted by bark extract treatment for 5 days, time-dependently enhanced the growth of NK-92MI cells with the maximal effect at 5th day of incubation. These results suggest that C. macrophylla, especially bark, has the potential for anticancer and immuno-modulatory activities.

• The Korean Journal of Mycology
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• v.35 no.2
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• pp.109-114
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• 2007

Oudemansiella radicata, edible and medicinal mushroom belonging to Agaricales of Basidiomycota, has been known to exhibit outstanding curative effects on the fungal infection and hypertension caused by high blood pressure. Neutral saline soluble (0.9% NaCl), hot water soluble and methanol soluble substances (hereinafter referred to Fr, NaCl, Fr. HW and Fr. MeOH, respectively) were extracted from fruiting body of the mushroom. In vitro cytotoxicity test showed that Fr. NaCl was not cytotoxic against NIH3T3 and Sarcoma 180 at the concentration of $10{\sim}1,000\;{\mu}g/ml$. Intraperitoneal injection with Fr. NaCl exhibited antitumor activity with life prolongation effect of $42.9{\sim}66.7%$ in mice inoculated with Sarcoma 180. Fr. NaCl improved the immunopotentiating activity of B lymphocyte by increasing the alkaline phosphatase activity by $1.4{\sim}3$ folds compared with controlled and LPS groups, respectively. Intraperitoneal injection with Fr. MeOH increased the numbers of peritoneal exudate cells and circulating leukocytes by 3.5 and 2.5 folds, respectively. Therefore, the antitumor effect exhibited on mouse Sarcoma 180 cells was likely due to immune-modulating activity of crude polysaccharides extracted from fruiting body of O. radicata.

• Korean Journal of Medicinal Crop Science
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• v.15 no.3
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• pp.162-169
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• 2007

Immune activities of two different extracts of Kadsura japonica Dunal. by typical extraction processes using water and ethanol at 60 $^{\circ}$C and 100 $^{\circ}$C were compared to them by ultrasofication system and through traditional fermemtation process. The fermented broth Kadsura japonica Dunal. definitely improved the growth of human B and T cell up to 30% and 22%, respectively, compared to the control. The secretion of TNF-${\alpha}$ and IL-60 was also enhanced by the addition of the fermented broth, up to 35%. NK cell activation was significantly improved up to 1.4 times higher than the case of adding other extracts. It was also found that this broth could yield higher nitric oxide production from macrophage than Lipopolysaccharides (LPS). It can be concluded that Kadsura japonica has immune activities and, in general, the culture broth from a conventional fermentation has higher immune activities, possibly by yielding immuno-modulatory compounds, not existed in typcial extraction systems as the result of HPLC analysis.

• The Journal of Internal Korean Medicine
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• v.39 no.6
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• pp.1244-1255
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• 2018

Objectives: The purpose of this study is to determine the stimulatory effects of herbal medicines extracts on cytokines release of immune response in immune cells, RAW 264.7 and TK-1 cell. Methods: In a total of 18 extracts, 9 water extracts and 9 ethanol extracts, of herbal medicines, the quantities of polyphenolic compounds were measured and anti-oxidation activities were determined by colorimetric assay. The herbal medicine extracts were treated on RAW 264.7 and TK-1, respectively, and then the releasing changes of tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6, and interleukin-10 from both immune cells were determined by the enzyme-linked immunosorbent assay. Results: The polyphenol contents were measured to be 1.56~0.64 mg/g of solids in the two types of extracts with 9 kinds of herbal medicines, while antioxidant activities were found to be 95.62~31.46% as compared with ascorbic acid control. In RAW 264.7 cells treated with herbal medicines extracts, the secretion of $TNF-{\alpha}$ increased to 1.31~1.18 fold, and the amounts of IL-6 were 68.4~97.9% compared with the control group treated with LPS alone. In particular, the secretion amount of anti-inflammatory cytokine IL-10 was suppressed by treatment using herbal medicine extracts. In the case of TK-1 cells, $TNF-{\alpha}$ secretion was suppressed according to the concentrations of herbal extract. The released amounts of IL-10 were shown at 10~40 pg/ml, and increased in a dose-dependent manner. Conclusions: Herbal medicines extracts act on macrophages inducing the secretion of inflammatory cytokine, thereby enhancing the activity of innate immunity. When acting on T cells involved in adaptive immunity, the secretion of anti-inflammatory cytokine is increased to induce the inhibition of the innate immune response.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.100-109
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• 2015

Controlling balance between T-helper type 1 (Th1) and T-helper type 2 (Th2) plays a pivotal role in maintaining the biological rhythm of Th1/Th2 and circumventing diseases caused by Th1/Th2 imbalance. Interleukin 4 (IL-4) is a Th2-type cytokine and often associated with hypersensitivity-related diseases such as atopic dermatitis and allergies when overexpressed. In this study, we have tried to elucidate the function of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (EC-18) as an essential modulator of Th1/Th2 balance. EC-18 has showed an inhibitory effect on the production of IL-4 in a dose-dependent manner. RT-PCR analysis has proved EC-18 affect the transcription of IL-4. By analyzing the phosphorylation status of Signal transducer and activator of transcription 6 (STAT6), which is a transcriptional activator of IL-4 expression, we discovered that EC-18 induced the decrease of STAT6 activity in several stimulated cell lines, which was also showed in STAT6 reporter analysis. Co-treatment of EC-18 significantly weakened atopy-like phenotypes in mice treated with an allergen. Collectively, our results suggest that EC-18 is a potent Th2 modulating factor by regulating the transcription of IL-4 via STAT6 modulation, and could be developed for immune-modulatory therapeutics.

• Korean Journal of Medicinal Crop Science
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• v.17 no.4
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• pp.257-265
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• 2009

Phosphatidylcholine was used to encapsulate aqueous extracts of Centella asiatica, and its biological activity was compared with another aqueous extracts. Nanoparticle of C. asiatica was made by encapsulation to w/o type spherical liposome which of aqueous extracts seized with oil phase as 78.2 nm average diameter. Cytotoxicity of the nanoparticle was measured on human skin fibroblast cells, CCD-986sk, and showed lower cytotoxicity on 1.0 mg/$m{\ell}$ of highest concentration as 28% than that of another extracts. The nanoparticle showed the highest promotion of human B and T cell growth up to 138% and 135%, respectively, compared to the control. and the NK cell growth was promoted up to 8% higher than the control in proportion to secretion of IL-6 and TNF-$\alpha$ from immune cell growth. Also nanoparticle showed highest inhibition activity of hyaluronidase on 1.0 mg/$m{\ell}$ of highest concentration as 60.5%. It seems that because of enhanced biological application of aqueous extracts on cell through nano-encapsulation process.

• Preventive Nutrition and Food Science
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• v.11 no.1
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• pp.54-60
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• 2006

The immunomodulatory effect of a new herbal preparation, HemoHIM, on the recovery from leukopenia induced by cyclophosphamide treatment was investigated. The HemoHIM was made up with an addition of the ethanol-insoluble fraction to the total water extract of Angelica Radix, Cnidii Rhizoma and Paeonia Radix. Daily oral administration of 100 mg/kg BW or 500 mg/kg BW HemoHIM accelerated the recovery from cyclophosphamide-induced leukopenia. HemoHIM increased the number of leukocytes and lymphocytes in the peripheral blood when compared with the cyclophosphamide-treated control. Moreover, the suppressed natural killer (NK) cell activity and interferon $(IFN)-{\gamma}$ secretion in the cyclophosphamide-treated mice were restored by the administration of HemoHIM. HemoHIM significantly reduced the abnormally heightened ratio of interleukin $(IL)-4/IFN-{\gamma}$ and immunoglobulin (Ig)E/IgG2a in the cyclophosphamide-treated mice. These results suggest that HemoHIM accelerates the recovery from leukopenia and alleviates the imbalanced T helper (Th)l/Th2 responses in the cyclophosphamide-treated mice. Additionally, HemoHIM was found to stimulate normal splenocytes to secrete not only Thl type cytokines such as $IFN-{\gamma}$ and IL-2, but also Th2 type cytokine IL-4. In conclusion, our results show that HemoHIM certainly has an influence on the balanced recovery of immune cells and the activation of their activities in the cyclophosphamide-treated mice.

• Molecules and Cells
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• v.39 no.10
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• pp.728-733
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• 2016

Mesenchymal stem cells (MSCs) effectively reduce airway inflammation and regenerate the alveolus in cigarette- and elastase-induced chronic obstructive pulmonary disease (COPD) animal models. The effects of stem cells are thought to be paracrine and immune-modulatory because very few stem cells remain in the lung one day after their systemic injection, which has been demonstrated previously. In this report, we analyzed the gene expression profiles to compare mouse lungs with chronic exposure to cigarette smoke with non-exposed lungs. Gene expression profiling was also conducted in a mouse lung tissue with chronic exposure to cigarette smoke following the systemic injection of human cord blood-derived mesenchymal stem cells (hCB-MSCs). Globally, 834 genes were differentially expressed after systemic injection of hCB-MSCs. Seven and 21 genes, respectively, were up-and downregulated on days 1, 4, and 14 after HCB-MSC injection. The Hbb and Hba, genes with oxygen transport and antioxidant functions, were increased on days 1 and 14. A serine protease inhibitor was also increased at a similar time point after injection of hCB-MSCs. Gene Ontology analysis indicated that the levels of genes related to immune responses, metabolic processes, and blood vessel development were altered, indicating host responses after hCB-MSC injection. These gene expression changes suggest that MSCs induce a regeneration mechanism against COPD induced by cigarette smoke. These analyses provide basic data for understanding the regeneration mechanisms promoted by hCB-MSCs in cigarette smoke-induced COPD.