• Toxicological Research
• /
• 제11권2호
• /
• pp.169-173
• /
• 1995

The effects of tumor necrosis factor alpha $(TNF-{\alpha})$ on growth and tubular formation of bovine aortic endothelial cells were examined using an in vitro angiogenesis model system. The growth of endothelial cells was enhanced in a dose-dependent manner when the cells were cultured with $TNF-{\alpha}$ for 3 days, but $TNF-{\alpha}$, at the concentration of 1 nM or higher, produced a growth inhibition of endothelial cells when the cells were cultured for 8 days. The endothelial cells incubated with $TNF-{\alpha}$ for 48-h exhibited a typical morphologic change. Then, they showed a fibroblastoid organization of overlapping, elongated, and spindle-shaped cells. $TNF-{\alpha}$, at the concentration of O. 1 nM or higher, inhibited the tubular formation of vascular endothelial cells in an in vitro anglogenesis model using a 3-dimensional culture system.

• Food Science and Biotechnology
• /
• 제18권5호
• /
• pp.1284-1287
• /
• 2009

Tumor necrosis factor (TNF)-${\alpha}$ is chronically elevated in adipose tissues of obese rodents and humans. Increased levels of TNF-${\alpha}$ have been implicated in both the induction of atherogenic adipokines, such as plasminogen activator inhibitor (PAI)-1, and the inhibition of the anti-atherogenic adipokine, adiponectin. In this study, we investigated the effects of trans-stilbene, piceatannol, rhaponticin, and piceid on the TNF-${\alpha}$-induced atherogenic changes of adipokines in 3T3-L1 cells. Exposure to TNF-${\alpha}$ for 24 hr increased PAI-1 secretion and decreased adiponectin secretion. Among stilbenoids, piceatannol significantly inhibited the increased secretion of PAI-1 induced by TNF-${\alpha}$. Adiponectin secretion decreased by TNF-${\alpha}$ was recovered after trans-stilbene and rhaponticin treatments. Our results showed that stilbenoids exerted different effects on TNF-${\alpha}$-induced changes in adipokines secretion in 3T3-L1 adipocytes according to their structural characteristics.

• 한국축산식품학회지
• /
• 제23권1호
• /
• pp.75-79
• /
• 2003

본 연구는 몽고 마유에서 pro-inflammatory cytokine(IL-l$\beta$, IL-6, TNF-a, IL-18)과 IL-1 receptor accessory를 Western blotting방법으로 확인하여 기능성 식품과 의약품 소재로 이 용하기 위한 기초 자료를 얻고자 실시하였다. 몽고 마유의 4개군 모두에서 IL-1, TNF-a가 17 kD에서 확인되었다. IL-18은 6~7 kD에서 확인할 수 있었다. 그리고, IL-1 receptor accessory를 55 kD에서 확인하였다. 그러나 탈지분유(Difco) 에서는 IL-l$\beta$, TNF-a를 확인할 수 없었으나, IL-6는 탈지분유(Difco) 및 몽고 마유에서 모두 60 kD에서 확인하였다. 이 와 같이 몽고 마유는 다양한 cytokine을 함유하고 있어서 기능성 식품 및 의약품 소재로 이용가치가 있다고 사료된다.

• Tuberculosis and Respiratory Diseases
• /
• 제76권6호
• /
• pp.261-268
• /
• 2014

Patients with immune-mediated inflammatory diseases (IMIDs) are increasingly being treated with anti-tumor necrosis factor (TNF) agents and are at increased risk of developing tuberculosis (TB). Therefore, diagnosis and treatment of latent TB infection (LTBI) is recommended in these patients due to the initiation of anti-TNF therapy. Traditionally, LTBI has been diagnosed on the basis of clinical factors and a tuberculin skin test. Recently, interferon-gamma releasing assays (IGRAs) that can detect TB infection have become available. Considering the high-risk of developing TB in patients on anti-TNF therapy, the use of both a tuberculin skin test and an IGRA should be considered to detect and treat LTBI in patients with IMIDs. The traditional LTBI treatment regimen consisted of isoniazid monotherapy for 9 months. However, shorter regimens such as 4 months of rifampicin or 3 months of isoniazid/rifampicin are increasingly being used to improve treatment completion rates. In this review, the screening methods for diagnosing latent and active TB before anti-TNF therapy in patients with IMIDs will be briefly described, as well as the current LTBI treatment regimens, the recommendations for managing TB that develops during anti-TNF therapy, the necessity of regular monitoring to detect new TB infection, and the re-initiation of anti-TNF therapy in patients who develop TB.

• Journal of Periodontal and Implant Science
• /
• 제35권3호
• /
• pp.799-811
• /
• 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.

• 대한의생명과학회지
• /
• 제28권3호
• /
• pp.192-194
• /
• 2022

The trophic factor Neuregulin-1 (NRG-1) plays a critical role in the development of the peripheral nervous system and the repair of nerve injuries. The regulation of neutrophil apoptosis by cytokine secretion from structural cells is an important process in inflammatory diseases, including asthma. This study aimed to investigate the relationship between NRG-1 and the alteration of neutrophil apoptosis by the regulation of cytokine release in the human lung epithelial BEAS-2B cells. Tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) induce the increase in the release of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1). NRG-1 alone had no effect on the secretion of IL-6, IL-8, and MCP-1. However, co-treatment of TNF-α and IFN-γ with NRG-1 inhibited the secretion of IL-6, IL-8, and MCP-1 that had been increased by TNF-α and IFN-γ. Treatment with NRG-1 did not have a direct effect on neutrophil apoptosis. Co-treatment of TNF-α and IFN-γ with NRG-1 was not effective on suppression of neutrophil apoptosis due to TNF-α and IFN-γ. The supernatant of BEAS-2B cells after co-treatment of TNF-α and IFN-γ with NRG-1 suppressed the inhibition of neutrophil apoptosis that had been caused due to the supernatant treated with TNF-α and IFN-γ. Taken together, NRG-1 has an anti-inflammatory effect in an inflammatory milieu by the regulation of cytokine secretion and neutrophil apoptosis.

• 대한한의학방제학회지
• /
• 제12권1호
• /
• pp.195-208
• /
• 2004

Objective: This study was conducted to investigate the effects of Aconiti Tuber on the plasma IL-6 and $TNF-{\alpha}$ level in mice stimulated by intracerebroventricular(I.C.V.) Injection of Lipopolysaccharide(LPS). Method: 6 mice were assigned to each of the normal group, the control group, and the experimental group. In the normal group only saline was administered intragastrically, and in the control group LPS was injected intracerebro-ventricularly 1 hr after intragastric administration of saline. In the experimental groups (Aconiti Tuber 0.5g/kg, Aconiti Tuber 1.0g/kg, Aconiti Tuber 3.0g/kg) each sample was administered intragastrically to mice 1 hr prior to the stimulation by LPS I.C.V. Injection. To measure the plasma IL-6 and $TNF-{\alpha}$ level of mice, their blood samples were collected from retro-orbital plexus, immediately centrifuged at $4^{\circ}C$, and plasma was removed and stored frozen at $-83^{\circ}C$ for later determination of plasma IL-6 and $TNF-{\alpha}$. Result : 1. LPS I.C.V. Injection increased plasma IL-6 level significantly in a dose-dependent manner compared with normal group(P<0.01). The plasma IL-6 concentration reached a significant maximal level about 1 hr after LPS I.C.V. Injection(P<0.001). LPS I.C.V. Injection increased plasma $TNF-{\alpha}$ level significantly in a dose-dependent manner(P<0.05). The plasma $TNF-{\alpha}$ concentration reached a significant maximal level about 1 hr after LPS I.C.V. Injection(P<0.001). 2. Sample A group to which Aconiti Tuber(0.5g/kg) was administered intragastrically 1 hr prior to the stimulation by LPS I.C.V. Injection showed insignificant lower plasma IL-6 level in 1 hr than control group(P<0.0635), and sample B group (Aconiti Tuber 1.0g/kg) showed significant lower plasma IL-6 level in 1 hr than control group(P〈0.05), and sample C group (Aconiti Tuber 3.0g/kg) showed significant lower IL-6 plasma level in 1 hr than control group(P<0.01). 3. sample A group to which Aconiti Tuber(0.5g/kg) was administered intragastrically 1 hr prior to the stimulation by LPS I.C.V. Injection showed insignificant lower plasma $TNF-{\alpha}$ level in 1 hr than control group(P>0.05), and Both sample B(1.0g/kg) and sample C(3.0g/kg) groups showed significant lower $TNF-{\alpha}$ plasma level in 1 hr than control group(P<0.01). These data revealed that Aconiti Tuber might have the anti inflammatory effect by reducing the plasma IL-6 and $TNF-{\alpha}$ level in a dose dependent manner in mice LPS I.C.V. Injection.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• 제10권1호
• /
• pp.11-19
• /
• 2007

목 적: 본 연구에서는 Henoch-Sch$\"{o}$nlein 자반증으로 진단된 환아들에서 급성기와 관해기에 TNF-${\alpha}$ 농도를 측정함으로써 Henoch-Sch$\"{o}$nlein 자반증의 발병과 임상양상의 발현에 있어 TNF-${\alpha}$의 의의를 평가하고, 각 환자에서 TNF-${\alpha}$ -308, -238 유전자 다형성의 유전자형과 대립유전자 빈도를 분석함으로써 Henoch-Sch$\"{o}$nlein 자반증의 발병에 있어 TNF-${\alpha}$ 유전자 다형성이 갖는 의의를 알아보고자 하였다. 방 법: 2004년 3월에서 2005년 11월까지 서울대병원 및 분당서울대병원 소아과에 내원하여 Henoch-Sch$\"{o}$nlein 자반증으로 진단받은 40명의 소아 환자를 대상으로 하였고, 건강한 소아 환아 32명을 대조군으로 하였다. 후향적인 의무기록지 검토를 통해 환아들의 임상양상을 조사하여 임상 점수를 평가하였다. 환자군에서 급성기와 관해기에 혈청 TNF-${\alpha}$ 농도를 측정하였다. 환자군과 대조군에서 혈액을 채취하여 TNF-${\alpha}$ -308과 -238 유전자 다형성을 조사하였다. 결 과: Henoch-Sch$\"{o}$nlein 자반증으로 진단된 40명 (남아 20명, 여아 20명)의 환아에서 급성기에 측정한 혈청 TNF-${\alpha}$ 농도는 $23.17{\pm}11.31$ pg/mL였으며, 증세가 소실된 후에 측정한 혈청 TNF-${\alpha}$ 농도는 $10.56{\pm}5.59$ pg/mL로서 유의하게 감소하였다(p=0.000). 혈청 TNF-${\alpha}$와 Henoch-Sch$\"{o}$nlein 자반증의 임상 점수 간에 유의한 상관관계는 없었다(r=0.310, p=0.070). TNF-${\alpha}$ -308 유전자형 빈도는 환자군에서 GG 80%, GA 20% 였으며, 대조군에서는 GG 93.8%, GA 6.2%로서 환자군에서 높은 GA 유전자형의 빈도를 보였지만 통계적인 유의성은 없었다(P=0.094). TNF-${\alpha}$ -238 유전자형 분포는 환자군에서 GG 97.5%, GA 2.5%였으며, 대조군에서는 GG 93.8%, GA 6.3%로서 두 군 사이에 통계적인 유의성이 없었다(p=0.429). 결 론: TNF-${\alpha}$는 Henoch-Sch$\"{o}$nlein 자반증의 발병에 중요한 역할을 하는 사이토카인으로 여겨지지만, TNF-${\alpha}$ -308, -238 유전자 다형성이 Henoch-Sch$\"{o}$nlein 자반증의 발병과 다양한 임상양상의 발현에 미치는 영향에 대해서는 뚜렷한 연관성이 확인되지 못하였기에 향후 지속적인 연구를 통하여 Henoch-Sch$\"{o}$nlein 자반증의 발병기전과 유전적 감수성을 밝히려는 시도가 이루어져야 할 것이다.

• 한국약용작물학회지
• /
• 제15권1호
• /
• pp.30-37
• /
• 2007

한국산 겨우살이 (Viscum album)는 면역 활성효과와 항암효과가 있다는 것으로 잘 알려져 있다. 본 연구에서는 한국산 겨우살이 추출물 M11C (비렉틴 구성물질)가 사람의 말초혈액 단구를 활성화시켜 tumor necrosis factor-alpha $(TNF-\alpha)$를 생산 분비하게 하는지를 규명하기 위해 실험에 이용되었다. 단구로부터 $TNF-\alpha$의 생산에 있어 M11C의 효과를 알기 위해 단구를 여러 농도 $(0-2000{\mu}g/m\ell)$의 M11C로 0.5-24시간 동안 자극한 후 배양액 MCM을 수거했다. 수거한 배양액 MCM을 $TNF-\alpha$에 민감한 L929 세포에 첨가한 후 L929 세포의 독성 정도를 MTT 기법으로 검사하였는데, 배양액 MCM이 L929 독성효과를 가졌으며, 이 MCM의 L929 세포 독성효과는 $TNF-\alpha$ 항체에 의해 거의 완전하게 억제되었다. 이러한 결과는 배양액 MCM에 $TNF-\alpha$가 존재함을 지적했으며, 또한 M11C가 단구를 자극해 $TNF-\alpha$를 생산하리라고 암시했었다. 이러한 암시를 확인하기 위해 immunoblotting 기법을 사용해 배양액 MCM에 존재하는 $TNF-\alpha$을 검사를 수행했다. 검사결과 배양액 MCM에 많은 량의 $TNF-\alpha$가 검출되었다. 이러한 $TNF-\alpha$ 검출량은 단구를 자극한 M11C의 농도와 자극시간에 비례해서 증가했다. 즉, 단구로부터 $TNF-\alpha$의 생산 분비량은 M11C의 농도와 자극시간에 의존적이었다. 이러한 M11C의 농도와 자극시간의 의존적 효과는 단구로부터 $TNF-\alpha$ mRNA 발현에도 같은 경향을 보였다. 결론적으로 한국산 겨우살이로부터 열탕 추출한 M11C가 면역활성제로 작용할 수 있음을 시사함과 동시에 한방탕제로 사용되는 한국산 겨우살이가 면역학적 효능을 가지고 있음을 말해주고 있다.

• 대한의생명과학회지
• /
• 제19권1호
• /
• pp.1-8
• /
• 2013

Parkin is known to be a tumor suppressor protein. Previously, we determined that parkin expression restores susceptibility to TNF-${\alpha}$-induced death of HeLa cells, a human cervical cancer cell line resistant to TNF-${\alpha}$-induced cell death. MMP-3 is a zinc-dependent protease recently reported to activate intracellular apoptotic signaling. In this study we examined the regulation of MMP-3 expression by parkin in TNF-${\alpha}$-treated HeLa cells. Furthermore, we investigated the signaling pathway involved in parkin-induced expression of MMP-3. We found that HeLa cells exhibit low levels of MMP-3 but is induced after introduction of the parkin gene into HeLa cells. Furthermore, MMP-3 expression increased further when parkin expressing cells were treated with TNF-${\alpha}$. Using chemical inhibitors of cell signaling pathways, we found that MEK-1 (PD98059), PI3K (LY294002), p38 MAPK (SB203580), and JNK inhibitors alleviated parkin-induced up-regulation of MMP-3. Finally, we show that TNF-${\alpha}$-induced cell death in parkin expressing cells is inhibited by using a MMP-3 inhibitor. These results suggest that parkin expression induces prolonged expression of MMP-3 via MEK-1, PI3K, MAPK, and JNK pathway in HeLa cells allowing the HeLa cells to become sensitive to TNF-${\alpha}$-induced cell death. These results implicate a role of MMP-3 in parkin-induced cell death in TNF-${\alpha}$ treated HeLa cells.