• Food Science of Animal Resources
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• v.21 no.4
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• pp.374-382
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• 2001

Lactoferrin(Lf) has the function of modulation in the host defense systems, including cytokine production and immune responses. We have tested the effect of Lf and Lf ydrolysates(Lf-H) on the productions of tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) and nitric oxide(NO) in macrophage cells. Lf from Korean native cattle(K-Lf) and hydrolyzed K-Lf(K-Lf-H) increased the production of TNF-${\alpha}$ in RAW264.7 cells with dose-dependency. Bovine Lf(B-Lf), human Lf(H-Lf), and its hydrolysates did not induce either TNF-${\alpha}$ production or NO production. On the other hand those didn\`t affect on the production of TNF-${\alpha}$ in lipopolysaccharide(LPS)-stimulated RAW264.7 cells. K-Lf induced the production of NO similar to its role on the TNF-${\alpha}$ production.

• Korean Journal of Medicinal Crop Science
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• v.18 no.2
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• pp.105-112
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• 2010

Korean Sophora japonica has been found to posses an anti-inflammatory activity. In this study, Korean Sophora japonica extract, rutin, was used to know whether rutin inhibits to produce inflammatory mediators NO and TNF-$\alpha$ from the mouse peritoneal macrophages that were treated an inflammatory agent LPS. The rutin-1 hr pretreated macrophages were incubated with LPS for 0.5~5 hrs, and then collected the supernatant and the cell lysate for measurements of the level of iNOS, NO, TNF-$\alpha$ mRNA, TNF-$\alpha$, and p-NF-${\kappa}B$. Minimal and maximal effective doses of the rutin on them were 1 and $100{\mu}g/ml$, respectively. The maximal effective dose of rutin certainly inhibted the productions of iNOS, NO, TNF-$\alpha$ mRNA, TNF-$\alpha$and p-NF-${\kappa}B$ from the LPS-treated macrophages (p<0.0001). Its $ED_{50}$ for inhibition of TNF-$\alpha$ mRNA and p-NF-${\kappa}B$ was $5{\mu}g/m{\ell}$, and for iNOS, NO, and TNF-$\alpha$ was $10{\mu}g/m{\ell}$. The rutin did not have any cytotoxic effect. As the results, the Sophora japonica rutin could be a good candidate for an anti-inflammatory action.

• The Journal of Korean Medicine
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• v.24 no.2
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• pp.138-147
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• 2003

Objectives : In this study, we investigated the mechanism by which Chelidonium majus (CM) regulates nitric oxide (NO) production. Methods : Using mouse peritoneal macrophages, the mechanism by which CM regulates NO or tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ production was examined. NO release was measured by the Griess method. $TNF-{\alpha}$ production was measured by the ELISA method. The protein extracts were prepared and samples were analyzed for the inducible NOS(iNOS) expression and nuclear factor kappa $B(NF-{\kappa}B)$ activation by Western blotting. Results : When CM was used in combination with recombinant $interferon-{\gamma}{\;}(rIFN-{\gamma})$, there was a marked cooperative induction of NO production. CM had an effect on NO production by itself. The expression of the iNOS gene was increased in $rIFN-{\gamma}$ plus CM-stimulated peritoneal macrophages and almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of $NF-{\kappa}B$. The $NF-{\kappa}B$ activation was increased in rIFN-{\gamma} plus CM-induced peritoneal macrophages. The increased production of NO from $rIFN-{\gamma}$ plus CM-stimulated peritoneal rnacrophages was decreased by the treatment with $N^{G}-monomethyl-{_L}-arginine{\;}(N^{G}MMA){\;}N^{\alpha}-Tosyl-Phe$ chloromethyl ketone (TPCK) , and was almost completely inhibited by pre-treatment with PDTC. Furthermore, treatment with CM alone or rIFN-{\gamma} plus CM in peritoneal macrophages caused a significant increase in $TNF-{\alpha}$ production. PDTC decreased CM-induced $TNF-{\alpha}$ production significantly. After CM treatment in HT-29 or AGS cells, cell viability decreased. Conclusions : These findings demonstrate that CM increases the production of NO and $TNF-{\alpha}{\;}by{\;}rIFN-{\gamma}-primed$ macrophages and suggest that NF-B plays a critical role in mediating these effects of CM.

• Journal of Periodontal and Implant Science
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• v.35 no.3
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• pp.799-811
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• 2005

This study was carried out to examine the potency of the three surface compo- nents from Porphyromonas gingivalis to stimulate the murine macrophage cell line RAW264.7 to synthesize the pro-inflammatory cytokine tumor necrosis factor alpha($TNF-{\alpha}$) and nitric oxide (NO). Lipopolysaccharide(LPS). lipid A-associated proteins(LAP) and saline-extractable surface -associated material(SAM) were isolated from P. gingivalis 381. $TNF-{\alpha}$ release into culture supernatants was determined by two-site ELISA. NO production was assayed by measuring the accumulation of nitrite in culture supernatants. Western blot analysis of iNOS and analysis of reverse transcription(RT)-PCR products were carried out. The surface components extracted from this bacterium were almost equally potent in stimulating release of $TNF-{\alpha}$ and NO by RAW264.7 cells. $TNF-{\alpha}$ that was being measured immunologically was due to activation of $TNF-{\alpha}$ gene transcription. The present study clearly shows that P. gingivalis surface components fully induced iNOS expression in RAW264.7 cells in the absence of other stimuli. The ability of P. gingivalis surface components to promote the production of $TNF-{\alpha}$ and NO may be important in the pathogenesis of inflammatory periodontal disease.

• Microbiology and Biotechnology Letters
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• v.27 no.1
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.2
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• pp.342-348
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• 2000

In this experiment, we show the effects of herbal plant extracts on the production of nitric oxide (NO) and TNF-$\alpha$. The extracts of Angelica gigas, Astragalus membranaceus, Acanthopanax sessiliflorus and Houttuynia cordata had no effect on NO synthesis by itself in mouse macrophage cell line (RAW264.7). However, the stimulation with these extracts in the presence of murine interferon-${\gamma}$(mIFN-${\gamma}$) resulted in increased NO synthesis. When these extracts were used in combination with mIFN-${\gamma}$, there were a marked cooperative induction of NO and TNF-$\alpha$ synthesis in a dose-dependent manner. The same results were obtained in the mouse peritoneal macrophages used. The optimal concentration of these extracts on NO synthesis was shown at 100$\mu\textrm{g}$/mL with 100U/mL of mIFN-${\gamma}$. NO synthesis was inhibited by NG-monomethyl-L-arginine. When cell lines were treated with extracts, the expression of inducible NO synthetase (iNOS) was markedly increased in RT-PCR analysis. In addition, synergy between mIFN-${\gamma}$ and extracts was dependent on extracts-induced tumor necrosis factor-$\alpha$(TNF-$\alpha$). These results suggest that water extracts of herbal plants can induce iNOS, NO and TNF-$\alpha$ synthesis of mouse macrophage cell line (RAW264.7) and peritoneal macrophages in combination with mIFN-${\gamma}$.

• The Journal of Korean Medicine
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• v.17 no.2 s.32
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• pp.227-236
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• 1996

The effect of Ligustrum Lucidum(LL) on the production of nitric oxide (NO) and superoxide by murine peritoneal macrophages were investigated. Stimulation of the cells with LL in the presence or absence of interferon-r(IFN-r) resulted in the increased accumulation of nitrite in the medium. To further examine the mechanism of LL induced. NO Synthesis, we evaluated the secretion of tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ by LL in murine macrophages. Treatment of LL increased the secretion of bioactive $TNF-{\alpha}$ in cultured medium. In addition, LL induced NO production was decreased by the treatment of anti-murine $TNF-{\alpha}$. neutralizing antibodies, indicating that LL induced superoxide production was decreased by the treatment of anti-murine $TNF-{\alpha}$ neutralizing antibodies. These data suggested that LL induced superoxide production was related to $TNF-{\alpha}$ secretion. In conclusion, our results indicates that LL may enhance innate immune response and be applied as a immunoregulating drug improving phagocytosis.

• Development and Reproduction
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• v.5 no.2
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• pp.101-106
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• 2001

Present study was aimed to verify the role of insulin and TNF-$\alpha$ in development of preimplantation embryos. Mouse morula were cultured for 40 hr in the presence or absence of insulin(400 ng/ml) and TNF-$\alpha$ (50 ng/ml). The morphological development, cell number of blastomeres per blastocyst, and mitogen activated protein kinase(MAPK) activity were examined. The developmental rate and cell number per embryo were the highest in insulin treatment group and the lowest in TNF-$\alpha$ treatment group. There was no significant difference in developmental rate between control and insulin plus TNF-$\alpha$ group. Taken together, it suggested that TNF-$\alpha$ impaired embryonic development and that insulin rescued developmental impairment imposed by TNF-$\alpha$. In blastocysts, insulin treatment significantly increased MAPK activity. TNF-$\alpha$ decreased the MAPK activity in a concentration-dependent manner. In the TNF-$\alpha$(50 ng/ml) -primed embryos, activation of MAPK by insulin was attenuated. In conclusion, these results suggest that there was a cross talk between insulin and TNF-$\alpha$ by means of activation of MAPK in preimplantation embryos and that insulin might rescue damage of embryos exposed to TNF-$\alpha$.

• Environmental Analysis Health and Toxicology
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• v.28
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• pp.12.1-12.5
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• 2013

Objectives The role of genetic polymorphisms of tumor necrosis factor-alpha (TNF-${\alpha}$) for lung cancer development was evaluated. Methods Genotypes of the TNF-${\alpha}$ polymorphisms, -1210C>T, -487A>G, -417A>G, IVS1+123G>A, and IVS3+51A>G, were determined in 616 lung cancer cases and 616 lung cancer-free controls. Results After adjusting for body mass index and smoking, each TNF-${\alpha}$ genotype or haplotype composed of five TNF-${\alpha}$ single nucleotide polymorphisms did not show an association with lung cancer risk (p>0.05). The statistical power was found to be 88.4%, 89.3%, 93.3%, 69.7%, and 93.9% for 1210C>T, -487A>G, -417A>G, IVS1+123G>A, and IVS3+51A>G, respectively. Furthermore, the effects of each SNP or haplotype on lung cancer risk were not found to be different according to the cell type of lung cancer (p>0.05). In the repeated analysis with only subjects without other diseases related to inflammation, there was also no association between polymorphisms or haplotypes of the TNF-${\alpha}$ gene and lung cancer risk (p>0.05). Conclusions This study found no association between common variants of the TNF-${\alpha}$ gene and lung cancer risk.

• Clinical and Experimental Pediatrics
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• v.48 no.7
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• pp.772-778
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• 2005

Purpose : Kawasaki disease(KD) is a systemic panvasculitis that causes coronary artery lesions. KD is accompanied by immunoregulatory abnormalities. Nitric oxide(NO) can induce relaxation of blood vessels by activating guanylate cyclase in smooth muscle cells and high levels of NO may result in coronary artery lesions. We investigated tumor necrosis factor$(TNF)-{\alpha}$ and NO production before and after intravenous immunoglobulin(IVIG) therapy to study the roles of NO and $TNF-{\alpha}$ in KD with coronary artery lesions. Methods : Serum levels of NO and $TNF-{\alpha}$ were measured in 24 patients with KD(group I, eight patients with normal coronary artery; group II, 16 patients with coronary artery lesions) and 23 controls(group III, 13 afebrile controls; group IV, 10 febrile controls). Blood samples from each subject were drawn before and after IVIG therapy and in the convalescent stage. Serum concentrations of NO and $TNF-{\alpha}$ were measured by enzyme linked immuno sorbent assay. Results : The NO levels before IVIG therapy were significantly higher in group II than in group I, group III and group IV. After IVIG therapy the levels of NO were significantly higher in group I and group II than in group III. The $TNF-{\alpha}$ levels before IVIG therapy were significantly higher in group I and group II than in group III. The serum $TNF-{\alpha}$ and NO levels were higher before IVIG therapy and decreased through the convalescent stage in KD patients. In the acute stage of KD patients with coronary artery lesions, serum NO levels significantly correlated with white blood cells (r=0.43, P<0.05). Conclusion : The serum concentration levels of $TNF-{\alpha}$ and NO were abnormally high in KD patients and NO concentrations were statistically higher in the KD patients with coronary artery abnormalities than those without coronary abnormality during the early stage of the KD. These results suggest NO may be involved in the development of coronary artery lesions.