• 대한수의학회지
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• 제45권4호
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• pp.501-505
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• 2005

Immu-Forte composed of chitosan, ${\beta}-glucan$, manno-oligosaccharide and pangamic acid was evaluated for its effectiveness as a nonspecific immunostimulator in mice. The effects of Immu-Forte were determined by analysis of cytokines using ELISA and phenotype of leukocyte subpopulations using monoclonal antibodies specific to mouse leukocyte differentiation antigens and flow cytometry. All T cells, all B cells, CD4 T cells, CD8 T cells, macrophages, IL-2, IL-4, IL-12 and IFN-r in Immu-Forte A-treated group increased in 1 months posttreatment and were significantly higher (p < 0.05) than that of control at 1 months posttreatment. All T cells, all B cells, CD4 T cells, CD8 T cells, macrophages and IL-2 in Immu-Forte EX-treated low and middle dose groups increased in 1 months posttreatment and were significantly higher (p < 0.05) than that of control at 1 months posttreatment. In the Immu-Forte soybean-treated group, NK cells and IL-4 were significantly higher in middle dose-treated group, and IL-2, IL-4 and IFN-r were significantly higher in low dose-treated group. In the Immu-Forte F-treated group, all T cells, all B cells, CD4 T cells, CD8 T cells, macrophages, NK cells, IL-2, IL-4, IL-12 and IFN-r in high dose-treated group and all T cells, all B cells, CD4 T cells, CD8 T cells, macrophages, IL-2, IL-4, IL-12 and IFN-r in middle dose-treated group and NK cells, IL-2, IL-4, IL-12 and IFN-r in low dose-treated group were significantly higher (p < 0.05) than that of control at 1 months posttreatment. In conclusion, this study has demonstrated that Immu-Forte had an immunostimulatory effect on mice through proliferation and activation of mouse immune cells.

• 한국약용작물학회지
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• 제17권1호
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• pp.54-60
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• 2009

This study was performed to improve immune activities of Rubus coreanus Miquel by encapsulation of nanoparticles. Immuno-activities of R. coreanus were investigated through aqueous extracts associated with process of water at $60^{\circ}C$. It showed high promotion of human B and T cells growth about 50%, compared to the case of other conditions. The secretion of IL-6 and TNF-${\alpha}$ was also enhanced as $2.44{\times}10^{-4}$pg/cell and $1.94{\times}10^{-4}$pg/cell, results by adding nano samples. NK cell activation was improved up to 29% higher than the conventional extraction process. The secretion of NO from macrophage showed 14.9 ${\mu}M$ on the nano-encapsulation process extracts, which was higher than others. The size of nanoparticles was in the range of 50${\sim}$300 nm, which can effect the penetration into the cells. It was clearly observed by real time confocal microscope.

• 대한약침학회지
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• 제20권3호
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• pp.158-172
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• 2017

Nigella sativa (N. sativa, family Ranunculaceae) is a medicinal plant that has been widely used for centuries throughout the world as a natural remedy. A wide range of chemical compounds found in N. sativa expresses its vast therapeutic effects. Thymoquinone (TQ) is the main component (up to 50%) in the essential oil of N. sativa. Also, pinene (up to 15%), p-cymene (40%), thymohydroquinone (THQ), thymol (THY), and dithymoquinone (DTQ) are other pharmacologically active compounds of its oil. Other terpenoid compounds, such as carvacrol, carvone, 4-terpineol, limonenes, and citronellol, are also found in small quantities in its oil. The main pharmacological characteristics of this plant are immune system stimulatory, anti-inflammatory, hypotensive, hepatoprotective, antioxidant, anti-cancer, hypoglycemic, anti-tussive, milk production, uricosuric, choleretic, anti-fertility, and spasmolytic properties. In this regard, we have searched the scientific databases PubMed, Web of Science, and Google Scholar with keywords of N. sativa, anti-cancer, apoptotic effect, antitumor, antioxidant, and malignancy over the period from 2000 to 2017. The effectiveness of N. sativa against cancer in the blood system, kidneys, lungs, prostate, liver, and breast and on many malignant cell lines has been shown in many studies, but the molecular mechanisms behind that anti-cancer role are still not clearly understood. From among the many effects of N. sativa, including its anti-proliferative effect, cell cycle arrest, apoptosis induction, ROS generation, anti-metastasis/anti-angiogenesis effects, Akt pathway control, modulation of multiple molecular targets, including p53, p73, STAT-3, PTEN, and $PPAR-{\gamma}$, and activation of caspases, the main suggestive anti-cancer mechanisms of N. sativa are its free radical scavenger activity and the preservation of various anti-oxidant enzyme activities, such as glutathione peroxidase, catalase, and glutathione-S-transferase. In this review, we highlight the molecular mechanisms of apoptosis and the anti-cancer effects of N. sativa, with a focus on its molecular targets in apoptosis pathways.

• Biotechnology and Bioprocess Engineering:BBE
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• 제7권2호
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• pp.67-75
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• 2002

The human complement receptor type 1 (CR 1, C3 b/C4b receptor) is a polymorphic membrane glycoprotein expressed on human erythrocytes, peripheral leukocytes, plasma and renal glomerular podocytes, which consists of transmembrane and cytoplasmic domains with 30 repeating homologous protein domains known as short consensus repeats (SCR). CR1 has been used as an inhibitor for inflammatory and immune system for the past several years. Recently; it is reported that CRl was found to suppress the hyper-acute rejection in xeno-transplantation and can be used to cure autoimmune diseases. A soluble form of CRl, called sCRl, is a recombinant CRl by cleaving the transmembrane domain at C-terminus and has been expressed in Chinese Hamster Ovary (CHO) cells. Several purification methods for sCR1 from CHO cells have been reported, but most of them require complicated steps at high cost. Moreover, such methods are mostly performed under the pH condition apt to denaturing sCR1 and causes sCRl losing its activity. We here report a rapid and efficient method to purify sCR1 from CHO cell. The new method consists of a two-stage of cell culture by cultivating cells in serum medium followed by serum-free medium, and a two-stage of column purification by means of heparin and gel filtration column chromatography. By using this novel method, sCR1 can be purified in a simple and effective way with high yield and purity, furthermore, the purified sCR1 was confirmed to retain its activity to suppress the complement activation in vivo and ex vivo.

• 셀메드
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• 제6권2호
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• pp.13.1-13.7
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• 2016

Fatigue is a common complaint and affects the quality of life in modern people. Physical stress may induce activation of certain immune cells. Fermented porcine placenta (FPP) has been used to alleviate fatigue. Inflammatory cytokines are produced by physical stress and results in symptoms of fatigue. However, the role of FPP on fatigue-associated inflammatory cytokine production has not been elucidated yet. Thus, we estimated the anti-fatigue effect of FPP and its active components, leucine (Leu) and lysine (Lys) in activated RAW264.7 macrophages and forced swimming test (FST) fatigue animal model. Pretreatment with FPP, Leu, or Lys significantly inhibited the lipopolysaccharide (LPS)-induced tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 production without inducing cytotoxicity on LPS-stimulated RAW264.7 macrophages. FPP, Leu, or Lys inhibited the production of nitric oxide and downregulated the expression of inducible nitric oxide synthase on LPS-stimulated RAW264.7 macrophages. Furthermore, caspase-1 activities increased by LPS were significantly reduced by FPP, Leu, or Lys. In the FST, inflammatory cytokine levels of the mice administrated with FPP, Lys, and Leu were significantly reduced compared with the control group at 21 days. Collectively, these results show that anti-fatigue effect of FPP and its active components, Leu and Lys might be derived from the down-regulating of inflammatory mediators.

• Animal cells and systems
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• 제15권3호
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• pp.227-233
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• 2011

The Nramp1/Slc11a1 locus encodes a proton-coupled divalent cation transporter, expressed in late endosomes/lysosomes of macrophages, that constitutes a component of the innate immune response to combat intracellular pathogens and it was shown to play an important role in regulating inherent immunity. The previously identified Z-DNA forming polymorphic repeat(GT)n in the promoter region of the human Nramp1 gene does act as a functional polymorphism influencing gene expression. Research has shown that INF-${\gamma}$, TNF-${\alpha}$, IL-$1{\beta}$ and bacteria LPS increase the level of Nramp1 expression. However, the molecular mechanism for Nramp1 gene regulation is unclear. In this research, bovine Nramp1 5'-flanking region (-1748~+769) was cloned and analyzed by bioinformatics. Then to find the core promoter and the cis-acting elements, deletion analysis of promoter was performed using a set of luciferase reporter gene constructs containing successive deletions of the bovine Nramp1 5'-flanking regions. Promoter activity analysis by the dual luciferase reporter assay system showed that the core promoter of Nramp1 was located at +58~-89 bp. Some positive regulatory elements are located at -89~-205 bp and -278~-1495 bp. And the repressor elements were in region -205~-278 bp, intron1 and -1495~-1748 bp. LPS-responsive regions were located at -1495~-1748 bp and -278~-205 bp. The present study provides an initial effort to explore the molecular mechanism of transcriptional activation of the bovine Nramp1 gene and should facilitate further studies to decode the complex regulatory process and for molecular breeding for disease resistance in bovines.

• Bulletin of the Korean Chemical Society
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• 제33권1호
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• pp.227-232
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• 2012

Galectins are generally believed to be potential candidates for use in the development of novel antiinflammatory agents or as selective modulators of the immune response. In particular, galectin-9 exhibits some of the extracellular functions, including cell aggregation, adhesion, chemoattraction, activation, and apoptosis. Tl-galectin (Tl-gal, galectin-9 homologue gene) was isolated from an adult worm of the Toxascaris leonina. The full-length Tl-gal gene, which was incorporated into pET-28a, was overexpressed in E. coli and purified by nickel affinity and gel filtration chromatographies. The purified Tl-gal was crystallized using the hangingdrop vapor-diffusion method. The crystal belonged to the tetragonal space group $P4_1$, with unit-cell parameters of a = b = $75.7\AA$ and c = $248.4\AA$. The crystals were obtained at $20^{\circ}C$ and diffracted to a resolution of $3.0\AA$. The asymmetric unit contained four molecules of Tl-gal, which gave a crystal volume per protein mass (Vm) of $2.8\AA^3Da^{-1}$ and a solvent content of 54.1%.

• The Korean Journal of Physiology and Pharmacology
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• 제14권4호
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• pp.235-240
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• 2010

Toll-like receptors (TLRs) functionally expressed in salivary epithelial cells, but their roles remain elusive. Among TLRs family, TLR3 is activated by dsRNA, a byproduct of viral infection. The aim of this study was to investigate the role of TLR3 in the inflammatory immune responses using HSG cells. Reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR and ELISA were performed to identify expression of TLRs and TLR3-mediated chemokine inductions. The chemotaxis assay of activated T lymphocytes was also performed. Treatment of HSG cells with polyinosinic: polycytidylic acid (poly(I:C)) significantly increased interferon-$\gamma$-inducible protein 10 (IP-10), interferoninducible T-cell $\alpha$ chemoattractant (I-TAC), and regulated on activation, normal T-cells expressed and secreted (RANTES) gene expressions in a concentration-dependent manner. Anti-TLR3 antibody blocked the increases of IP-10 and I-TAC genes. Poly(I:C)-induced increases of IP-10 and I-TAC were also confirmed at protein levels from cell lysates, but their release into extracellular medium was detected only in IP-10. We found that the culture media from HSG cells stimulated with poly(I:C) significantly increases T lymphocyte migration. Our results suggest that TLR3 plays an important role in chemokine induction, particularly IP-10, in salivary epithelial cells.

• Journal of Microbiology and Biotechnology
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• 제24권1호
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• pp.127-131
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• 2014

While searching for lactic acid bacteria that can restore aging-impaired immune responses, we isolated the Toll-like receptor (TLR) 2/NF-${\kappa}B$-activating strain Lactobacillus plantarum HY7712 from kimchi and investigated its immunomodulating effect in whole-body ${\gamma}$-irradiated mice. Exposure to HY7712 strongly activated NF-${\kappa}B$ signaling in RAW264.7 cells, but inhibited lipopolysaccharide-stimulated NF-${\kappa}B$ activation. Moreover, HY7712 protected against the downregulation of interferon (IFN)-${\gamma}$ and upregulation of interleukin (IL)-13 caused by ${\gamma}$-irradiation in mice. In mice, ${\gamma}$-irradiation impaired NK-cell activity against YAC-1 tumor cells, but following HY7712 exposure, the activity of NK cells was restored to 91.5% of the level measured in control mice (p < 0.05). These findings suggest that HY7712 activates the TLR2/NF-${\kappa}B$ signaling pathway and protects against the impairment of NK-cell activity caused by ${\gamma}$-irradiation or aging.

• Journal of Ginseng Research
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• 제42권4호
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• pp.476-484
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• 2018

Background: Korean Red Ginseng (steamed and dried white ginseng, Panax ginseng Meyer) is well known for enhancing vital energy and immune capacity and for inhibiting cancer cell growth. Some clinical studies also demonstrated a therapeutic potential of ginseng extract for treating lung inflammatory disorders. This study was conducted to establish the therapeutic potential of ginseng saponins on the lung inflammatory response. Methods: From Korean Red Ginseng, 11 ginsenosides (Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1, Rg2, Rg3, and Rh2) were isolated. Their inhibitory potential and action mechanism were evaluated using a mouse model of lung inflammation, acute lung injury induced by intranasal lipopolysaccharide administration. Their anti-inflammatory activities were also examined in lung epithelial cell line (A549) and alveolar macrophage (MH-S). Results: All ginsenosides orally administered at 20 mg/kg showed 11.5-51.6% reduction of total cell numbers in bronchoalveolar lavage fluid (BALF). Among the ginsenosides, Rc, Re, Rg1, and Rh2 exhibited significant inhibitory action by reducing total cell numbers in the BALF by 34.1-51.6% (n = 5). Particularly, Re showed strong and comparable inhibitory potency with that of dexamethasone, as judged by the number of infiltrated cells and histological observations. Re treatment clearly inhibited the activation of mitogen-activated protein kinases, nuclear factor-${\kappa}B$, and the c-Fos component in the lung tissue (n = 3). Conclusion: Certain ginsenosides inhibit lung inflammatory responses by interrupting these signaling molecules and they are potential therapeutics for inflammatory lung diseases.