• IMMUNE NETWORK
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• v.12 no.3
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• pp.113-117
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• 2012

FasL, perforin, $TNF{\alpha}$, IL-1 and NO have been considered as effector molecule(s) leading to ${\beta}$-cell death in autoimmune diabetes. However, the real culprit(s) of ${\beta}$-cell destruction have long been elusive despite intense investigation. Previously we have suggested $IFN{\gamma}/TNF{\alpha}$ synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of $IFN{\gamma}$ and $TNF{\alpha}$ but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. $IFN{\gamma}$ treatment conferred susceptibility to $TNF{\alpha}$-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that $IFN{\gamma}/TNF{\alpha}$ synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by $IFN{\gamma}$ treatment in human islet cells. Taken together, we suggest that $IFN{\gamma}/TNF{\alpha}$ synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.6
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• pp.636-642
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• 2007

Background: CpG DNA plays an important role in immune cell function. This study examined whether the temporal control of toll-like receptor (TLR)9 by CpG DNA can regulate the expression of matrix metalloproteinase-9(MMP-9). Methods and materials: Macrophages were cultured in the presence of 10% FBS. For the various MMP genes analysis, RT-PCR and real-time PCR were performed. In addition, zymography assay performed for the MMP activity. The phosphorylation assay did for the ERK1/2 and NF${\kappa}B$ activation, and luciferase promoter assay was for the NF${\kappa}B$ activity. Results: CpG DNA induced the mRNA expression of MMP-2, MMP-9, and MMP-13, but not of MMP-7, MMP-8, and MMP-12, in a time-dependent manner. Especially, the mRNA expression of MMP-9 was strongly induced by CpG DNA using real-time RT-PCR. The TLR9 inhibitor, chloroquine, suppressed CpG DNA-induced MMP-9 expression and its activity. Moreover, CpG DNA induced the phosphorylation of ERK and the inhibition of ERK by U0126 suppressed CpG DNA-induced MMP-9 expression and its activity. CpG DNA stimulated $I{\kappa}B-{\alpha}$ degradation and luciferase activity. In addition, pretreatment of SN-50, the inhibitor of NF${\kappa}B$, strongly blocked the CpG DNA-induced MMP-9 expression and activity. Conclusion: These observations suggest that CpG DNA may play important roles in the activation of macrophages by regulating the production of MMP-9 via the sequential TLR9-ERK-NF${\kappa}B$ signaling pathway.

• Biomedical Science Letters
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• v.24 no.1
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• pp.30-34
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• 2018

Silver (Ag) has been widely used in commercial products and medical fields since ancient times because of its antibacterial effect. It is harmless and non-toxic to the human body. For this reason, recent research has actively evaluated antimicrobial activity using silver (Ag). In this study, we investigated the inhibitory effect of a silver-based compound, silver phosphate ($Ag_3PO_4$) on the growth of Staphylococcus aureus and the activation of human immunity. First, the inhibitory effect of $Ag_3PO_4$ on the growth of Staphylococcus aureus was confirmed by a growth curve and a colonyounting method. As a result, the growth inhibitory effect increased as the concentration of $Ag_3PO_4$ increased. Specifically, treatment with $5{\mu}g/mL$ of $Ag_3PO_4$ resulted in no bacteria growth, and the colony-counting method showed a remarkable inhibition. In addition, the expression of cytokine IL-8 by $Ag_3PO_4$ was examined to investigate the cellular immune system activation by $Ag_3PO_4$. After pretreatment of Staphylococcus aureus for 1 hour with $50{\mu}g/mL$ $Ag_3PO_4$, an increased IL-8 mRNA expression resulted. In cells treated with $Ag_3PO_4$, we found that the expression of IL-8 was enhanced in a time-dependent fashion compared to non-treated cells. These results indicate that $Ag_3PO_4$ induces antimicrobial activity against Staphylococcus aureus and activates human immunity. These results are expected to contribute to the future study of the mechanism of silver (Ag) and silver-based compounds in relation to antibacterial activity.

• BMB Reports
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• v.50 no.9
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• pp.472-477
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• 2017

The transcription repressor Bach2 has been proposed as a regulator of T cell quiescence, but the underlying mechanism is not fully understood. Given the importance of interleukin-2 in T cell activation, we investigated whether Bach2 is a component of the network of factors that regulates interleukin-2 expression. In primary and transformed $CD4^+$ T cells, Bach2 overexpression counteracted T cell receptor/CD28- or PMA/ionomycin-driven induction of interleukin-2 expression, and silencing of Bach2 had the opposite effect. Luciferase and chromatin immunoprecipitation assays revealed that Bach2 binds to multiple Maf-recognition element-like sites on the interleukin-2 proximal promoter in a manner competitive with AP-1, and thereby represses AP-1-driven induction of interleukin-2 transcription. Thus, this study demonstrates that Bach2 is a direct repressor of the interleukin-2 gene in $CD4^+$ T cells during the immediate early phase of AP-driven activation, thereby playing an important role in the maintenance of immune quiescence in the steady state.

• Journal of Haehwa Medicine
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• v.19 no.2
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• pp.145-151
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• 2011

Backgrounds: Multidisciplinary approaches including surgery, chemotherapy, and radiation therapy are currently being performed to target various cancers in Western Medicine. However, some cancers still remain difficult to battle, which has long attracted many scientists for the discovery of new agents to fight cancers. Ginseng is one of the herbs used in Oriental Medicine including Korea, China and Japan. We have further investigated ginseng for its anticancer effect. Objective: This is a comprehensive review summary of anticancer effect of ginseng and ginsenoids as a possible agent for future cancer treatment. Methods: Data were retrieved from two web sites; www.pubmed.com and www.riss.kr, and authorized texts concerning anticancer effects of ginseng. From collected data, information on anticancer effect of ginseng was thoroughly sorted, restructured, then assessed. Results: Panax Ginseng C.A. Meyer belongs to Araliaceae Panax family, a perennial prairie plant with its root known as Ginseng Radix. Ginseng induces anticancer effect through cell cycle arrest, acceleration of apoptosis, anti-angiogenesis, and suppression of metastasis. Anticancer effect of ginseng may be due to single compound or multi-compound actions. Many studies report involvement of immune mechanisms of cytokines, Natural Killer (NK) cells, macrophages and some antibodies in enhancing anticancer effect of ginseng. In near future, possibility of applying these mechanisms into clinical trials is convinced. There were some important findings on saponin in ginsenoids in reviewing for this article; First, eradication of metastatic tumors were influenced by macrophage activation. Second, suppression of malignant melanoma cell metastasis to lung were induced by macrophage and NK cell activation in spleen with red ginseng acidic polysaccharide (RGAP). Third, final metabolites of M1, M4 had exerted anticancer effect of ginseng. Conclusion: Unknown anticancer mechanisms of ginseng have been studied for many years up until now. Ginseng is comprised of multiple bio-chemical compounds that create complex pharmaceutical interactions. Therefore, for its proper usage and safe prescription, studies on different types of ginseng and patients' susceptibility to ginseng according to their constitution and stages of the disease should be further pursued. More efforts are needed to understand the anticancer mechanisms of ginseng as well.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.11
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• pp.1664-1674
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• 2016

This research analyzed the effect of ${\beta}$-glucan that is expected to alleviate the production of the inflammatory mediator in macrophagocytes, which are processed by the lipopolysaccharide (LPS) of Escherichia. The incubated layer was used for a nitric oxide (NO) analysis. The DNA-binding activation of the small unit of nuclear factor-${\kappa}B$ was measured using the enzyme-linked immunosorbent assay-based kit. In the RAW264.7 cells that were vitalized by Escherichia coli (E. coli) LPS, the ${\beta}$-glucan inhibited both the combatant and rendering phases of the inducible NO synthase (iNOS)-derived NO. ${\beta}$-Glucan increased the expression of the heme oxygenase-1 (HO-1) in the cells that were stimulated by E. coli LPS, and the HO-1 activation was inhibited by the tin protoporphyrin IX (SnPP). This shows that the NO production induced by LPS is related to the inhibition effect of ${\beta}$-glucan. The phosphorylation of c-Jun N-terminal kinases (JNK) and the p38 induced by the LPS were not influenced by the ${\beta}$-glucan, and the inhibitory ${\kappa}B-{\alpha}$ ($I{\kappa}B-{\alpha}$) decomposition was not influenced either. Instead, ${\beta}$-glucan remarkably inhibited the phosphorylation of the signal transducer and activator of transcription-1 (STAT1) that was induced by the E. coli LPS. Overall, the ${\beta}$-glucan inhibited the production of NO in macrophagocytes that was vitalized by the E. coli LPS through the HO-1 induction and the STAT1 pathways inhibition in this research. As the host immune response control by ${\beta}$-glucan weakens the progress of the inflammatory disease, ${\beta}$-glucan can be used as an effective immunomodulator.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.1
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• pp.16-22
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• 2016

The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influence the intestinal environment. Intestinal alkaline phosphatase (IAP) is an important apical brush border enzyme that is influenced by these factors. IAP dephosphorylates bacterial lipopolysaccharides (LPS), unmethylated cytosine-guanosine dinucleotides, and flagellin, reducing bacterial toxicity and consequently regulating toll-like receptors (TLRs) activation and inflammation. It also desphosphorylates extracellular nucleotides such as uridine diphosphate and adenosine triphosphate, consequently reducing inflammation, modulating, and preserving the homeostasis of the intestinal microbiota. The apical localization of IAP on the epithelial surface reveals its role on LPS (from luminal bacteria) detoxification. As the expression of IAP is reported to be downregulated in piglets at weaning, LPS from commensal and pathogenic gram-negative bacteria could increase inflammatory processes by TLR-4 activation, increasing diarrhea events during this phase. Although some studies had reported potential IAP roles to promote gut health, investigations about exogenous IAP effects or feed additives modulating IAP expression and activity yet are necessary. However, we discussed in this paper that the critical assessment reported can suggest that exogenous IAP or feed additives that could increase its expression could show beneficial effects to reduce diarrhea events during the post weaning phase. Therefore, the main goals of this review are to discuss IAP's role in intestinal inflammatory processes and present feed additives used as growth promoters that may modulate IAP expression and activity to promote gut health in piglets.

• IMMUNE NETWORK
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• v.6 no.3
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• pp.117-122
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• 2006

Background: Caveolin, a family of integral membrane proteins are a principal component of caveolae membranes. In this study, we investigated the effect of p38 kinase on differentiation and on inflammatory responses in sodium nitroprusside (SNP)-treated chondrocytes. Methods: Rabbit articular chondrocytes were prepared from cartilage slices of 2-week-old New Zealand white rabbits by enzymatic digestion. SNP was used as a nitric oxide (NO) donor. In this experiments measuring SNP dose response, primary chondrocytes were treated with various concentrations of SNP for 24h. The time course of the SNP response was determined by incubating cells with 1mM SNP for the indicated time period $(0{\sim}24h)$. The cyclooxygenase-2 (COX-2) and type II collagen expression levels were determined by immunoblot analysis, and prostaglandin $E_2\;(PGE_2)$ assay was used to measure the COX-2 activity. The tyrosine phosphorylation of caveolin-1 was determined by immunoblot analysis and immunostaining. Results: SNP treatment stimulated tyrosine phosphorylation of caveolin-1 and activation of p38 kinase. SNP additionally caused dedifferentiation and inflammatory response. We showed previously that SNP treatment stimulated activation of p38 kinase and ERK-1/-2. Inhibition of p38 kinase with SB203580 reduced caveolin-1 tyrosine phosphorylation and COX-2 expression but enhanced dedifferentiation, whereas inhibition of ERK with PD98059 did not affect caveolin-1 tyrosine phosphorylation levels, suggesting that ERK at least is not related to dedifferentiation and COX-2 expression through caveolin-1 tyrosine phosphorylation. Conclusion: Our results indicate that SNP in articular chondrocytes stimulates dedifferentiation and inflammatory response via p38 kinase signaling in association with caveolin-1 phosphorylation.

• IMMUNE NETWORK
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• v.10 no.6
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• pp.212-218
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• 2010

Backgroud: The stem bark of Kalopanax pictus (KP) has been used in traditional medicine to treat rheumatoidal arthritis, neurotic pain and diabetes mellitus in China and Korea. In this study, the mechanism responsible for anti-inflammatory effects of KP was investigated. Methods: We examined the effects of KP on NO production, nitric oxide synthase (iNOS) and HO-1 expression, NF-${\kappa}B$, Nrf2 and MAPK activation in mouse peritoneal macrophages. Results: The aqueous extract of KP inhibited LPS-induced NO secretion as well as inducible iNOS expression, without affecting cell viability. KP suppressed LPS-induced NF-${\kappa}B$ activation, phosphorylation and degradation of $I{\kappa}B-{\alpha}$, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Furthermore, KP induced HO-1 expression and Nrf2 nuclear translocation. Conclusion: These results suggest that KP has the inhibitory effects on LPS-induced NO production in macrophages through NF-${\kappa}B$ suppression and HO-1 induction.

• Proceedings of the Korean Institute of Surface Engineering Conference
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• 2017.05a
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• pp.78-78
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• 2017

Pure Titanium and alloy have been widely used in dental implants and orthopedics due to their excellent mechanical properties, biocompatibility and corrosion resistance. However, due to the biologically inactive nature of Ti metal implants, it cannot bind to the living bone immediately after transplantation into the body. In order to improve the bone bonding ability of titanium implants, many attempts have been made to alter the structure, composition and chemical properties of titanium surfaces, including the deposition of bioactive coatings. The PEO method has the advantages of short experiment time and low cost. These advantages have attracted attention recently. Recently, many metal ions such as silicon, magnesium, zinc, strontium, and manganese have received attention in this field due to their impact on bone regeneration. Silicon (Si) in particular has been found to be essential for normal bone and cartilage growth and development. Zinc (Zn) plays very important roles in bone formation and immune system regulation and promotes bone metabolism and growth. Manganese (Mn) is an essential trace metal found in all tissues and is required for normal amino acid, lipid, protein and carbohydrate metabolism. The objective of this work was research on the corrosion behavior of Si, Zn and Mn-doped hydroxyapatite on the PEO-treated surface. Anodized alloys was prepared at 270V~300V voltage in the solution containig Zn, Si, and Mn ions. Ion release test was carried out using potentidynamic and AC impedance method in 0.9% NaCl solution. The surface characteristics of PEO treated Ti-6Al-4V alloy were investigated using XRD, FE-SEM, AFM and EDS.