• 한국미생물·생명공학회지
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• 제27권1호
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• pp.28-34
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• 1999

Ganoderan (GAN), an immunomodulating ${\beta}$-glucan from mushroom Ganoderma lucidum, was evaluated for its ability to induce formation of nitric oxide (NO), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) and transforming growth factor (TGF-${\beta}$) from rat Kupffer cell in vitro. Hepatic macrophages activated by GAN significantly elevated concentration of NO and TNF-${\alpha}$ in cultured medium, but not significantly elevated that of TGF-${\beta}$. GAN-activated Kupffer cells secrete 14.9${\mu}$M (p<0.01) of NO and 2619.5${\rho}$g/ml (p<0.01) of TNF-${\alpha}$after 36hr of incubation at 37$^{\circ}C$. The results revealed that GAN enhanced 4-fold production of NO and 19 fold formation of TNF-${\alpha}$ compared to the control. The proliferation of GAN-activated Kupffer cells was inhibited as compared with its negative control. Comparing the activity among glucans derived from microorganisms, highly branched zymosan, glucomannan from Saccharomyces cerevisiae, significantly increased TNF-${\alpha}$ and NO production. These results indicate that the ${\beta}$-glucan from G. lucidum activates rat Kupffer cell and secretes NO and TNF-${\alpha}$. It also suggest that rat Kupffer cell posses certain receptor for ${\beta}$-anomeric glucan.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1649-1654
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• 2016

Tea derived from the leaves and buds of Camellia sinensis (Theaceae) is consumed worldwide. Green tea contains various components with specific health-promoting effects, and is believed to exert protective effects against diseases including cancer, diabetes and hepatitis, as well as obesity. Of the various tea components, the polyphenol catechins have been the subject of extensive investigation and among the catechins, (-)-epigallocatechin gallate has the strongest bioactivity in most cases. Our research group has postulated that hepatocyte nuclear factor-$4{\alpha}$, sterol regulatory element-binding proteins, and tumor necrosis factor-${\alpha}$ are targets of green tea constituents including (-)-epigallocatechin gallate for their anti-diabetes, anti-obesity, and anti-hepatitis effects, respectively. Published papers were reviewed to determine whether the observed changes in these factors can be correlated with anti-cancer effects of green tea. Two major action mechanisms of (-)-epigallocatechin gallate have been proposed; one associated with its anti-oxidative properties and the other with its pro-oxidative activity. When reactive oxygen species are assumed to be involved, our findings that (-)-epigallocatechin gallate downregulated hepatocyte nuclear factor-$4{\alpha}$, sterol regulatory element-binding proteins, and tumor necrosis factor-${\alpha}$ may explain the anti-cancer effect of green tea as well. However, further studies are required to elucidate which determinant directs (-)-epigallocatechin gallate action as an anti-oxidant or a pro-oxidant for favorable activity.

• 대한한의학회지
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• 제30권6호
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• pp.35-43
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• 2009

Objectives: Hwangryunhaedok-tang (HRHDT), a prescription composed of four herbs, has been wi dely used in Oriental Medicine for the treatment of cerebral infarction. However, the mechanisms by which the herbal formula affects on the production of pro- and anti-inflammatory cytokines in cerebral infarction patients remain unknown yet. Methods: The levels of pro- and anti-inflammatory cytokines, including tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6, IL-10, and TGF-${\beta}1$ were determined in peripheral blood mononuclear cells (PBMCs) from cerebral infarction patients under our experimental conditions. Results: The secretory levels of pro- and anti-inflammatory cytokines, including tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6, and IL-10 were significantly increased in phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from cerebral infarction patients. However, pretreatment with HRHDT significantly inhibited the secretion of pro- and anti-inflammatory in PBMCs. Also, HRHDT induced a significant increase of transforming growth factor (TGF)-b1 in PBMCs. Conclusions: These data indicate that HRHDT may be beneficial in the suppression of inflammatory processes of cerebral infarct through suppression of TNF-$\alpha$, IL-$1{\beta}$, IL-6, and IL-10 and induction of TGF-${\beta}1$.

• 한방재활의학과학회지
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• 제31권1호
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• pp.1-16
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• 2021

Objectives This study was designed to evaluate the effects of Danggwisu-san (Dangguixu-san, DG) on bone repair from femur fracture in mice. Methods Mice were randomly divided into 4 groups (normal, control, positive control and DG 300 mg/kg-treated group). In order to investigate the effects of DG on gene expressions in experimental animals with fracture, we measured the levels of bone morphogenetic protein-2 (BMP2), cyclooxygenase-2 (COX2), Sox9, collagen type II alpha 1 chain (Col2a1), runt-related transcription factor 2 (Runx2), osterix genes. After the cytotoxicity test, we analyzed the levels of expression of osteocalcin and Runx2, and tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine. The process of fusion in the fracture was also investigated by gross examination. Results Through in vivo BMP2, COX2 gene expression significantly decreased. Sox9 significantly increased. Col2a1, Runx2, osterix gene expression also increased as well, but there was no statistical significance. The degree of unilateral fracture fusion investigated by gross examination was significantly faster than those of the other groups. Through in vitro the level of TNF-α in macrophages was increased by DG in a dose-dependent mannerand and 250 and 500 ㎍/mL showed statistical significance. Osteocalcin and Runx2 genes expressions increased when DG was treated in osteoblasts. Conclusions DG promotes the healing of the fracture through the expression of bone repair-related genes and TNF-α production. This study may set the foundation for the clinical application of DG to the patients with bone fractures.

• Journal of Microbiology and Biotechnology
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• 제27권12호
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• pp.2156-2164
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• 2017

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered as an antitumor agent owing to its ability to induce apoptosis of cancer cells without imparting toxicity toward most normal cells. TRAIL is produced in poor yield because of its insoluble expression in the cytoplasm of E. coli. In this study, we achieved soluble expression of TRAIL by fusing maltose-binding protein (MBP), b'a' domain of protein disulfide isomerase (PDIb'a'), or protein disulfide isomerase at the N-terminus of TRAIL. The TRAIL was purified using subsequent immobilized metal affinity chromatography and amylose-binding chromatography, with the tag removal using tobacco etch virus protease. Approximately 4.5 mg of pure TRAIL was produced from 125 ml flask culture with a purification yield of 71.6%. The endotoxin level of the final product was $0.4EU/{\mu}g$, as measured by the Limulus amebocyte lysate endotoxin assay. The purified TRAIL was validated and shown to cause apoptosis of HeLa cells with an $EC_{50}$ and Hill coefficient of $0.6{{\pm}}0.03nM$ and $2.41{\pm}0.15$, respectively. The high level of apoptosis in HeLa cells following administration of purified TRAIL indicates the significance and novelty of this method for producing high-grade and high-yield TRAIL.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10209-10215
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• 2015

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

• Clinical and Experimental Pediatrics
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• 제53권1호
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• pp.41-47
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• 2010

목 적 : 아디포넥틴은 혈관벽의 염증 반응을 억제시켜 혈관의 remodeling을 조절하는 내인적 조절 인자이다. 그러나 가와사키병에서 아디포넥틴의 역할은 알려져 있지 않다. 이 연구의 목적은 혈중 아디포넥틴 농도와 IL-6, $TNF-{\alpha}$, lipid profile, C 반응 단백 등 몇몇 parameter들의 상관 관계를 알아보고, 아디포넥틴과 심기능의 연관성을 밝히는 것이다. 방 법 : 실험군은 가와사키병으로 진단받은 총 22명의 환아(급성기 22명, 아급성기 환아 20명)를 대상으로 하였고, 대조군은 총 31명(열성 질환이 있는 환아 13명, 건강아 18명)을 대상으로 하였다. 두 군 모두에서 혈액 검사와 TDI를 실시하였다. 결 과 : C 반응 단백은 대조군에 비해 가와사키 군에서 유의하게 증가되었다. 아디포넥틴, IL-6, $TNF-{\alpha}$ 치는 두 군 간에 유의한 차이가 없었다. 하지만 아디포넥틴과 C 반응 단백, 혈소판 수치 사이에 유의한 음의 상관 관계가 있었다. TDI로 측정한 수축기 심근 속도와 A 심근 속도가 급성기에서 아급성기, 대조군에 비해 유의하게 심근 속도가 감소됨이 확인되었고, 아디포넥틴과는 양의 상관 관계를 보였다. 결 론 : 급성 가와사키 환아에서 혈중 아디포넥틴 농도가 낮을수록 염증 반응이 심하며 좌심실의 기능이 떨어짐을 확인할 수 있었다.

• 생명과학회지
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• 제18권9호
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• pp.1207-1211
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• 2008

Pro-inflammatory cytokine인 종양괴사인자-$\alpha$ (TNF-$\alpha$)는 B형 간염바이러스(HBV) 감염에 대한 면역반응의 중요한 매개인자이다. TNF-$\alpha$의 생산은 전사수준에서 주로 조절되며, TNF-$\alpha$ promoter 다형성은 TNF-$\alpha$ 유전자 발현을 변화시키기 때문에, TNF-$\alpha$ promoter 다형성이 만성 HBV 감염의 병태생리에 영향을 미칠 가능성이 높다. 그러므로, 본 연구에서는 TNF-$\alpha$ promoter 다형성과 만성 HBV 감염의 연관성을 조사하였다. 본 연구는 만성 HBV 감염환자 181명, HBV 감염이 자연적으로 치유된 201명, 그리고 건강한 대조군 170명을 대상으로 하였다. TNF-$\alpha$ promoter의 -308G/A와 -238G/A 다형성은 PCR-RFLP법을 통하여 분석하였다. 분석결과, 환자군에서 -308과 -238 유전자형의 분포는 자연치유군 및 건강대조군에서의 분포와 통계적인 차이를 보이지 않았다(p>0.05). 또한, 그룹 간에 allele frequency도 통계적 차이가 없었다(p>0.05). 따라서, 본 연구의 결과는 한국인에서 TNF-$\alpha$ -308과 -238 promoter 다형성은 만성 B형 간염 바이러스 감염의 발생과 연관성이 없음을 시사한다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제15권1호
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• pp.44-51
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• 2012

Purpose: Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) polymorphism has been suggested to play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in obese adults, and known to be a mediator of insulin resistance. In this study, we evaluated the role of TNF-${\alpha}$ promoter polymorphisms and insulin resistance in the development of NAFLD in obese children. Methods: A total of 111 obese children (M:F=74:37; mean age, $11.1{\pm}2.0$ yrs) were included. The children were divided into 3 groups: controls (group I, n=61), children with simple steatosis (group II, n=17), and children with non-alcoholic steatohepatitis (group III, n=33). Serum TNF-${\alpha}$ levels, homeostasis model assessment of insulin resistance (HOMA-IR), and TNF-${\alpha}$ -308 and -238 polymorphisms were evaluated. Results: There were no differences in TNF-${\alpha}$ polymorphism at the -308 or the -238 loci between group I and group II + III ($p$=0.134 and $p$=0.133). The medians of HOMA-IR were significantly different between group I and group II + III ($p$=0.001), with significant difference between group II and group III ($p$=0.007). No difference was observed in the HOMA-IR among the genotypes at the -308 locus ($p$=0.061) or the -238 locus ($p$=0.207) in obese children. Conclusion: TNF-${\alpha}$ promoter polymorphisms at the -308 and -238 loci were not significantly associated with the development of NAFLD in children; nevertheless, insulin resistance remains a likely essential factor in the pathogenesis of NAFLD in obese children, especially in the progression to NASH.

• Journal of Periodontal and Implant Science
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• 제48권5호
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• pp.284-294
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• 2018

Purpose: Epithelial barrier dysfunction is involved in the pathophysiology of periodontitis and oral lichen planus. Estrogens have been shown to enhance the physical barrier function of intestinal and esophageal epithelia, and we aimed to investigate the effect of estradiol (E2) on the regulation of physical barrier and tight junction (TJ) proteins in human oral epithelial cell monolayers. Methods: HOK-16B cell monolayers cultured on transwells were treated with E2, an estrogen receptor (ER) antagonist (ICI 182,780), tumor necrosis factor alpha ($TNF{\alpha}$), or dexamethasone (Dexa), and the transepithelial electrical resistance (TER) was then measured. Cell proliferation was measured by the cell counting kit (CCK)-8 assay. The levels of TJ proteins and nuclear translocation of nuclear factor $(NF)-{\kappa}B$ were examined by confocal microscopy. Results: E2 treatment increased the TER and the levels of junctional adhesion molecule (JAM)-A and zonula occludens (ZO)-1 in a dose-dependent manner, without affecting cell proliferation during barrier formation. Treatment of the tight-junctioned cell monolayers with $TNF{\alpha}$ induced decreases in the TER and the levels of ZO-1 and nuclear translocation of $NF-{\kappa}B$. These $TNF{\alpha}-induced$ changes were inhibited by E2, and this effect was completely reversed by co-treatment with ICI 182,780. Furthermore, E2 and Dexa presented an additive effect on the epithelial barrier function. Conclusions: E2 reinforces the physical barrier of oral epithelial cells through the nuclear ER-dependent upregulation of TJ proteins. The protective effect of E2 on the $TNF{\alpha}-induced$ impairment of the epithelial barrier and its additive effect with Dexa suggest its potential use to treat oral inflammatory diseases involving epithelial barrier dysfunction.