• Journal of Ginseng Research
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• 제33권1호
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• pp.1-7
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• 2009

우리 몸의 많은 기관을 비롯하여 장기들은 반복적이거나 혹은 급성 스트레스를 이겨내지 못하고 만성 스트레스로 이어질 경우 질병이 생기게 된다. 특히 강하고 지속적인 스트레스에 노출되면 뇌의 해마 수지상 세포(hippocampal dendrites)가 위축되거나 크기가 작아진다. 이렇게 스트레스로 인하여 증가된 글루코 코티코이드 호르몬은 뉴런 흥분제인 glutamate를 유도하거나 에너지 대사를 변형시켜 신경 독작용을 일으킨다. 이러한 연속적인 반응은 TNF-$\alpha$ convertase(TACE)를 활성화시켜 TNF-$\alpha$가 분비되도록 하여 전사 조절자인 NF-${\kappa}B$가 핵내로 전이되고 신경 손상을 일으키는 iNOS와 COX-2와 같은 효소를 유도한다. 이런 산화적 스트레스의 상위조절인자 TACE는 스트레스에 의한 여러 가지 염증성 질환 및 숙주방어에서 가장 중요한 조절자인 TNF-alpha를 수용체로부터 "유리(shedding)" 시키는 역할을 한다. 따라서 이런 신호 전달계를 자극하는 TACE의 발현 양과 이로 인한 지속적인 처리과정이 중요한 문제로 대두되고 있다. 특히 여러 스트레스 중에서 고정화 스트레스 및 신체적 구속 스트레스에 대한 연구는 뇌에서 산화물 생성을 증가시키지만 인삼이 뇌의 산화물질 생성에 어떤 영향을 미치는지 체계적인 연구가 진행된 바 없다. 따라서 염증을 매개하는 TNF-alpha의 생산에 중요한 역할을 하는 TACE의 발현 조절 및 TNF-alpha 신호전달을 연구함으로써 인삼의 항산화 기전을 분자 수준에서 규명할 수 있게 될 것으로 기대된다.

• 동의신경정신과학회지
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• 제9궈1호
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• pp.73-82
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• 1998

Substantial evidence has accumulated that Alzheimer's disease is associated with a local inflammatory reaction in senile plaques which may be immunemediated, and includes extensive Brain Neuroglial invasion, lymphocytic infiltration, cytokine deposition. Tumor necrosis factor a (TNF-a) is a cytokine which plays an important immunoenhancing role in the local acute and chronic inflammatory response in response to a variety of stimuli. The neuropeptide, substance P, can stimulate secretion of TNF-a from Brain Neuroglial cells. Neuroglia have substance P receptors in the central nervous system. WQ investigated whether RADIX ASPARAGI inhibits secretion of TNF-a from primary cultures of Brain Neuroglial cells containing both astrocyte (∼90%) and microglia (∼10%). RADIX ASPARAGI dose-dependently inhibited the TNF-a secretion induced by substance P plus lipopolysaccharide (LPS). In cultures enriched for micoglia (>95% pure). LPS stimulated the secretion of TNF-a but substance P caused no enhancement. Because there was no synergism between substance P and LPS in the microglial cultures it is resonable to substance P madiated enhancement of TNF-a secretion. IL-1 is a modulator of TNF-a secretion in the immune system. Also IL-1 has been shown to elevate TNF- a secretion from LPS-stimulated Brain Neuroglial cells while having no effect on Brain Neuroglial cells in the absence of LPS. We therfore investigated whether IL-1 mediates the RADIX ASPARAGI inhibition of TNF-a secretion form primary Brain Neuroglial cells. Treatment of RADIX ASPARAGI to mixed cultures stimulated with both substance P and LPS decreased TNF-a secretion to the level observed with LPS alone. These results indicate that RADIX ASPARAGI possess strong antiinflammatory activity in the cental nervous system by inhibition of inflammatory cytokines secretion from Brain Neuroglial cells.

• 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.

• Tuberculosis and Respiratory Diseases
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• 제48권4호
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• pp.513-521
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• 2000

Background : TNF may play an important role(central mediator) in the development of an acute respiratory distress syndrome. Since TNF induced lung injury in the acute respiratory distress syndrome and abnormalities in surfactant function have been described in acute respiratory distress syndrome, the authors investigated the effects of TNF on the regulation of surfactant protein A, B and C mRNA accumulation. Methods : The effects of TNF on gene expression of surfactant protein A, B, and C were analyzed using filter hybridization, 12 and 24 hours after intravenous injection of TNF in rats. Results : 1. The accumulation of SP-A mRNA in the TNF treated group (12 and 24 hours after TNF injection) was significantly decreased by 22.9% and 27.4%, respectively, compared to the control group (P<.025, P<.025). 2. The accumulation of SP-B mRNA in 24 hours after TNF treated group was significantly decreased by 20.5% compared to that of the control group(P<.01). 3. The accumulation of SP-C mRNA in 12 hours after TNF treated group was significantly decreased by 31% the compared to that of the control group(P<.01). Conclusions : These findings indicate the marked inhibitory effects of tumor necrosis factor on surfactant proteins expression in vivo. This finding. in turn, supports the idea of inhibitory effects of tumor necrosis factor on surfactant proteins expression as it relates to pathogenesis of acute respiratory distress syndrome.

• Korean Journal of Acupuncture
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• 제32권3호
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• pp.116-123
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• 2015

Objectives : The present study was designed to investigate effects and molecular mechanisms of Atractylodes macrocephala Koidzumi extracts(AMK) on the improvement of adipocyte dysfunction induced by TNF-${\alpha}$ in 3T3-L1 adipocytes. We examined whether AMK could directly influence the inflammation and insulin resistance in 3T3-L1 adipocytes. Methods : Potential roles of AMK in the lipolysis, production of inflammatory adipokines and ROS, expression and phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein, and expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ were investigated in this study. Results : Our data demonstrated that TNF-${\alpha}$ significantly increased lipolysis, levels of MCP-1, IL-6, and ROS and phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein, while TNF-${\alpha}$ reduced the expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ in adipocytes, suggesting that TNF-${\alpha}$ induced a condition with the occurrence of inflammation and insulin resistance. Those alterations induced by TNF-${\alpha}$ were prevented by the treatment of AMK. AMK down-regulated the phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein and up-regulated the expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ on TNF-${\alpha}$-induced inflammation and insulin resistance. Conclusions : Thus, our results indicate that AMK can be used to prevent from the TNF-${\alpha}$-induced adipocyte dysfunction through MAPK, $NF{\kappa}B$ and $PPAR{\gamma}$ pathways.

• 생명과학회지
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• 제17권1호
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• pp.45-50
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• 2007

세포 배양액에 tetracycline이 없는 경우 FADD를 발현하면서 사멸하는 평활근세포 (FADD-SMC)에서 분비하는 $TNF-\alpha$의 활성을 조사하였다. 배양액에 tetracycline이 없는 경우 FADD-SMC는 약 1000 pg/ml의 $TNF-\alpha$를 분비하였다. $TNF-\alpha$를 포함하는 배양액을 분리하고, 이 배양액을 정상세포에 처리한 결과 인산화한 p38 MAPK와 nuclear, factor, kappa B (NF-kB)의 활성이 증가하였다. 또한 이 배양액을 L929 세포에 처리하는 경우 세포독성이 발생하였다. NF-kB, p38 MAPK 그리고 L929 세포에 대찬 효과는 배양액에서 suluble TNF receptor를 이용하여 $TNF-\alpha$를 제거하는 경우 감소하였다.

• 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.

• 약학회지
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• 제42권1호
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• pp.82-88
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• 1998

The effect of hepatoprotective agents and bile acids on tumor necrosis factor-alpha, (TNF-${\alpha}$) production in murine and human macrophage cell line (RAW264.7 and U937) was inve stigated. The hepatoprotective agents including silymarin and its major component, silybin, significantly inhibited TNF-alpha production in a concentration dependent manner ($IC_50$ of silybin=67.7${\mu}g$/ml (140.3${\mu}g$M)). In differentiated U937 cells, especially, silybin showed more effective inbitory activity ($IC_50$=35.1${\mu}g$g/ml (72.7${\mu}g$M)). These results suggest that silymarin and silybin may inhibit TNF-alpha production in the process of hepatic diseases in human. However, biphenyldimethyl dicarboxylate (DDB) was not effective. In the case of bile acids, chenodeoxycholic acid (CDCA) showed a concentration dependent inhibitory effect on TNF-alpha production ($IC_50$ of CDCA= 71.5${\mu}g$g/ml (182.1${\mu}g$M)). In contrast, glycine or taurine conjugated form (G-CDCA or T-CDCA) restored to the control level or significantly increased TNF-${\alpha}$ production. And also ursodeoxycholic acid (UDCA) and its conjugated forms (G-UDCA and T-UDCA) showed a variety of patterns on TNF-${\alpha}$ production by changes of functional groups and concentration. These results also indicate that bile acids may regulate TNF-${\alpha}$ production in normal hepatic function or disease conditions.

• 대한의생명과학회지
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• 제27권4호
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• pp.223-230
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• 2021

Tumor necrosis factor alpha (TNF-α) is a principal regulator of inflammation and immunity. The proinflammatory properties of TNF-α can be attributed to its ability to activate the enzyme cytosolic phospholipase A₂ (cPLA₂), which generates potent inflammatory lipid mediators, eicosanoids. L-glutamine (Gln) plays physiologically important roles in various metabolic processes. We have reported that Gln has a potent anti-inflammatory activity via rapid upregulation of mitogen-activated protein kinases (MAPKs) phosphatase (MKP)-1, which preferentially dephosphorylates the key proinflammatory enzymes, p38 MAPK and cytosolic phospholipase A₂ (cPLA₂). In this study, we have investigated whether Gln could inhibit TNF-α-induced cPLA₂ activation. Gln inhibited TNF-α-induced increases in cPLA₂ phosphorylation in the lungs and blood levels of the cPLA₂ metabolites, leukotrine B4 (LTB4) (lipoxygenase metabolite) and prostaglandin E2 (PGE2) (cyclooxygenase metabolite). TNF-α increased p38 and cPLA₂ phosphorylation and blood levels of LTB4 and PGE2, which were blocked by the p38 inhibitor SB202190. Gln inhibited TNF-α-induced p38 and cPLA₂ phosphorylation and production of the cPLA₂ metabolites. Such inhibitory activity of Gln was no longer observed in MKP-1 small interfering RNA-pretreated animals. Our data indicate that Gln inhibited TNF-α-induced cPLA₂ phosphorylation through MKP-1 induction/p38 inhibition, and suggest that the utility of Gln in inflammatory diseases in which TNF-α plays a major role in their pathogenesis.

• Tuberculosis and Respiratory Diseases
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• 제46권5호
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• pp.636-644
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• 1999

연구배경 : 종양괴사인자(tumor necrosis factor ; TNF)는 다양한 생물학적 기능을 가지고 있는바, 그 중 생체 외에서 증명된 뚜렷한 항암 효과로 말미암아 최근 항암유전자요법의 중요한 대상으로 관심을 모으고 있다. 그러나 TNF의 세포독성의 기전에 대해서는 확실히 밝혀진 바가 없고 반응성 산소기가 관여할 것임을 시사하는 연구들이 있었으나, 항산화제에 의해서 TNF의 세포독성이 감소되는 지에 대해서는 상충되는 결과가 있었다. 본 연구는 TNF의 세포독성의 기전에서 반응성 산소기의 역할을 알아보기 위해 TNF 감수성 종양세포에 여러 가지 항산화제를 전처치한 후의 TNF 세포독성이 감소하는 지를 대조군과 비교하였다. 방 법 : TNF에 비교적 감수성을 보이는 세포주인 WEHI164(murine fibrosarcoma cell line)와 ME180(human cervix cancer cell line)을 배양하여 각각 3가지 항산화제로 전처치한 것과 대조군을 TNF 10ng/ml로 세포독성을 유도하고 그 정도를 MTT(dimethylthiazolyl-diphenyltetrazolium bromide) assay를 이용하여 세포독성 정도를 측정 비교하였다. 결 과 : 항산화제를 전처치하지 않은 대조군에서는 WEHI164 세포와 ME180 세포가 각각 $92.2{\pm}2.8%$와 $59.9{\pm}7.0%$의 세포독성을 보였고, TMTU를 전처지한 군은 각각 $91.4{\pm}3.7%$와 $74.6{\pm}7.0%$, PMZ을 전처치한 군은 $90.2{\pm}2.5%$와 $62.5{\pm}5.7%$, BHT을 전처치한 군은 $93.2{\pm}1.3%$와 $66.3{\pm}6.1%$로 세포독성의 유의한 감소는 없었다. 결 론 : 종양세포에 대한 TNF의 세포독성은 항산화제에 의해 감소되지 않으며 따라서 TNF의 세포독성은 반응성 산소기에 의한 것이 주된 기전은 아니라고 판단된다.