• 한국축산식품학회지
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• 제21권4호
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• pp.374-382
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• 2001

Lf는 cytokines의 생성 및 면역반응 등의 생체 방어적 기능을 하는 물질로 알려져 있다. 본 연구에서는 Lf과 Lf-h에 의해 macrophage에서 TNF-$\alpha$와 NO 생성에 미치는 효과를 조사하였다. K-Lf 및 K-Lf-h는 단독으로 TNF-$\alpha$의 생성을 증가시켰으며, Lf의 농도에 따라 그 생성량이 증가하였다. LPS와 함께 작용시켰을 경우에는 큰 효과가 없는 것으로 나타났으나, 세포 성장률은 증가시켰다. 그러나 B-Lf, H-Lf, 그리고 이들의 가수분해물들은 단독으로는, RAW264.7 cell을 자극하여 TNF-$\alpha$나 NO의 생성을 증가시키지 못하였다. 또한, K-Lf는 그 자체만으로 TNF-$\alpha$에서 보여준 것처럼 NO생성에 영향을 미치며 농도가 높아짐에 따라 NO 생성을 증가시키는 경향을 보여주었다.

• 한국약용작물학회지
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• 제18권2호
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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.

• 대한한의학회지
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• 제24권2호
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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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• 제35권3호
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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.

• 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.

• 한국식품영양과학회지
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• 제29권2호
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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-${\gamma}$.

• 대한한의학회지
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• 제17권2호
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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.

• 한국발생생물학회지:발생과생식
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• 제5권2호
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• pp.101-106
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• 2001

Insulin과 tumor necrosis factor alpha(TNF-$\alpha$)에 의한 초기 배아 발생의 조절기작을 알아보고자 생쥐의 상실배를 대상으로 이들이 첨가된 배양액에서 형태발생, 세포증식을 조사하고, 포배에서 mitogen activated protein kinase(MAPK, ERK1/2)의 활성 변화에 미치는 영향을 조사하였다. Insulin은 상실배의 체외발생 및 포배내 할구 수를 대조군에 비해 유의하게 증가시켰으며, TNF-$\alpha$는 발생율을 유의하게 감소시켰다. Insulin은 TNF- $\alpha$에 의한 배아 발생율 감소를 완화하였다. TNF-$\alpha$는 농도에 의존적으로 MAPK 활성을 감소시켰으며, insulin은 포배에서 MAPK의 활성을 유의하게 증가시킨 반면 TNF-$\alpha$는 처리농도에 의존적으로 MAPK 활성을 감소시켰다. 50 ng/ml 농도의 TNF-$\alpha$를 전처리한 포배에서는 insulin에 의한 MAPK 활성의 증가가 저해되었다. 이러한 결과로부터 생쥐의 착상전 초기 배아 발생조절에 insulin과 TNF-$\alpha$ 사이에 MAPK를 경유하는 cross talk이 존재함을 확인하였고 insulin은 TNF-$\alpha$ 에 의한 배아의 손상을 억제하는 것으로 사료된다.

• Environmental Analysis Health and Toxicology
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• 제28권
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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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• 제48권7호
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• pp.772-778
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• 2005

목 적 : 가와사키병은 면역 조절 인자의 이상을 동반하는 전신적 혈관염으로 관상동맥질환을 초래한다. NO는 혈관내 평활근의 granulocyte cyclase의 기전에 영향을 미쳐 혈관의 이완을 유발하는 역할을 하며 과다하게 분비될 경우 혈관의 변성을 초래하는 것으로 알려져 있다. 본 저자들은 가와사키병에서 NO와 $TNF-{\alpha}$의 혈중 농도를 측정하여 관상동맥질환 발생과 연관이 있는지 알아보기 위해 본 연구를 실시하였다. 방 법 : 가와사키병 환아 24명을 관상동맥 확장이 없는 군(1군)과 관상동맥 확장이 있는 군(2군)으로 분류하여 각 군의 임상 양상과 면역글로불린 투여 전과 후, 회복기에서의 NO, $TNF-{\alpha}$의 혈중 농도를 면역효소법(ELISA)으로 측정하여 비교하였다. 대조군으로는 같은 시기에 내원한 열이 없는 정상 대조군(3군) 13명과 열이 있는 대조군(4군) 10명으로 하였다. 결 과 : 면역글로불린 투여 전의 혈중 NO는 1군($13.2{\pm}5.7{\mu}mol/L$), 2군($20.4{\pm}10.7{\mu}mol/L$)과 4군($12.4{\pm}8.9{\mu}mol/L$)이 3군($3.1{\pm}1.4{\mu}mol/L$)보다 높았고 2군이 1군과 4군에 비해 유의하게 높았다(P<0.05). $TNF-{\alpha}$는 2군($858.4{\pm}934.0pg/mL$)에서 3군($8.7{\pm}2.3pg/mL$)과 4군($226.7{\pm}647.2pg/mL$)에 비해 유의하게 높았으며 1군($522.4{\pm}859.6pg/mL$)도 3군에 비해 높았다(P<0.05). 면역글로불린 투여 후 NO는 1군, 2군과 4군이 3군에 비해 유의하게 높았으며 $TNF-{\alpha}$는 각 군별로 유의한 차이가 없었다. 가와사키병 관상동맥 확장군과 비확장군 모두에 있어 NO와 $TNF-{\alpha}$의 혈중 농도가 면역글로불린 투여 전에 가장 높았고 면역글로불린 투여 후와 회복기로 갈수록 감소하였다. 또한 관상동맥 확장군에서 백혈구 수치와 혈청 NO는 유의한 양의 상관관계가 있었다(r=0.430). 결 론 : 가와사키병 환자에 있어 NO, $TNF-{\alpha}$의 혈중 농도가 유의하게 높았으며 NO의 농도가 관상동맥이 확장된 환자에서 비 확장군보다 의미있게 높은 것으로 보아 NO가 관상동맥질환에 관여할 것으로 생각한다.