• 한국식품영양과학회지
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• 제40권5호
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• pp.635-641
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• 2011

본 연구는 TNF-${\alpha}$로 자극된 HUVEC에서 녹차씨껍질 EtOAC 추출물이 초기 동맥경화 과정에 중요한 역할을 하는 염증매개인자와 세포부착물질에 미치는 영향을 분석하였다. 녹차씨껍질 EtOAC 추출물의 NO 생성능은 TNF-${\alpha}$만을 처리한 control군에 비해 증가시키는 것을 알 수 있었다. $100{\mu}g$/mL 농도에서는 녹차씨껍질 EtOAC 추출물은 세포독성을 보이지 않았으며 염증매개인자인 TNF-${\alpha}$ 수준 및 세포부착물질인 VCAM-1과 MCP-1의 생성을 억제하였다. 뿐만아니라, 녹차씨껍질 EtOAC 추출물은 총 항산화능은 증가되는 경향을 보였다. 이상의 결과에서, 녹차씨껍질 EtOAC 추출물은 HUVEC에서 TNF-${\alpha}$로 인한 총 항산화능의 수준을 향상시켜 염증생성인자인 TNF-${\alpha}$ 수준 및 세포부착물질인 VCAM-1과 MCP-1의 생성을 억제하여 동맥경화 초기반응을 억제하는데 기여할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제54권2호
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• pp.199-209
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• 2003

연구배경 : 만성폐쇄성폐질환 환자의 체중감소는 질환의 자연경과로 조직의 산소소모량을 최소로 유지하기 위한 일종의 신체적응과정으로 이해하였다. 그러나 만성폐쇄성폐질환 환자의 체중감소가 에너지대사량 증가와 관계 있고, 체중감소가 심한 환자들은 폐기능의 감소정도와 상관없이 이환율과 사망률이 증가한다는 연구결과가 보고된 후, 영양학적인 부분에 대하여 관심을 가지게 되었다. 저자들은 만성폐쇄성폐질환자 중 만성기관지염 환자와 폐기종 환자의 폐기능과 체성분을 측정하여 혈중 leptin농도 및 $TNF-{\alpha}$ system 과의 관계를 비교하여, 체중감소와의 관계를 알아보았다. 방 법 : 미국흉부학회의 진단기준에 따라 1초간 노력성 호기량이 예측치의 80% 미만이고, 노력성 폐활량에 대한 1초간 노력성 호기량의 비 ($FEV_1$/FVC)가 70% 미만인 41명의 환자를 대상으로 하였다. Kco가 60미만인 경우를 폐기종으로, 80이상인 경우를 만성기관지염으로 분류하였으며, 체성분 분석, 및 혈중 leptin농도, 그리고 $TNF-{\alpha}$ system의 활성도를 측정하였다. 결 과 : 만성기관지염 환자 및 폐기종 환자의 혈중 leptin농도는 각각 $1378.1{\pm}428.3pg/ml/kg$, $947.0{\pm}441.0pg/ml/kg$로 만성기관지염 환자가 유의하게 높았으며, 이들 값을 체지방량으로 교정하였을 때도 $180.9{\pm}57.7pg/ml/kg$, $108.5{\pm}39.4pg/ml/kg$로 만성기관지염 환자가 유의하게 높았다 (p<0.05). 혈중 $TNF-{\alpha}$ system 은 $TNF-{\alpha}$, sTNF-R75는 양 군에서 차이가 없었으나, sTNF-R55는 폐기종 환자군에서 $920.4{\pm}116.4pg/ml$로 만성기관지염 환자보다 유의하게 높았다 (p<0.05). 혈중 leptin농도는 체지방량 및 체질량지수와 상관관계가 있었으며, sTNF-R55는 체지방량이나 체질량지수와 관계가 없었다. 또한 sTNF-R55의 활성도는 혈중 leptin농도와도 무관하였다. 결 론 : 만성기관지염에 비하여 체중감소가 심한 폐기종의 체중감소에는 혈중 leptin보다는 $TNF-{\alpha}$ system이 관계할 것으로 생각되며, $TNF-{\alpha}$ system은 혈중 leptin와는 무관하게 작용할 것으로 생각한다. 그러나 앞으로 이에 대하여 더 많은 환자를 대상으로 한 연구가 있어야 하겠으며, 만성폐쇄성폐질환자의 체중변화에 영향을 줄 수 있는 영양섭취, 운동량, 안정시 에너지소모량 및 다른 사이토카인 등과의 관계에 대한 연구도 이루어져야 할 것이다.

• International Journal of Oral Biology
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• 제43권1호
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• pp.29-35
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• 2018

It is noted that chalcone derivatives have characteristic diverse pharmacological properties, and that precise evidence has been growing that they could regulate a tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) induced insulin resistance. The purpose of the present investigation is to elucidate the effects of the identified chalcone derivatives on adipogenesis, and to find the underlying mechanism of action in that case. Consequently, we first investigated whether the chalcone derivatives could affect the identified $PPAR{\gamma}$-induced transcriptional activity on the proliferator-activated receptor response elements (PPRE) at target promoters, and find that trans-chalcone most significantly increased the $PPAR{\gamma}$-induced transcriptional activity. Additionally, we confirmed that there were up-regulatory effects of trans-chalcone during the adipogenesis and lipid accumulation, and on the mRNA of adipogenic factors in 3T3-L1 cells. Next, we examined the effect of trans-chalcone on the inhibition induced by $TNF-{\alpha}$ on adipogenesis. To that end, we noted that the treatment with trans-chalcone attenuated the effect of $TNF-{\alpha}$ mediated secretion of various adipokines that are involved in insulin sensitivity. For this reason, we noted that this study clearly demonstrates that trans-chalcone enhanced adipogenesis, in part, by its potent effect on $PPAR{\gamma}$ activation and by its reverse effect on $TNF-{\alpha}$.

• BMB Reports
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• 제40권2호
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• pp.290-294
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• 2007

Saxatilin is a disintegrin known to inhibit tumor progression in vivo and in vitro. The role of saxatilin in cancer cell invasion was examined by a modified Boyden chamber assay in MDAH 2774 human ovarian cancer cell line. Saxatilin (50 nM) significantly inhibited cancer cell invasion induced by tumor necrosis factor-$\alpha$ (TNF-a$\alpha$). Saxatilin also reduced MMP-9 mRNA levels in cancer cells in a dosedependent manner. In addition, TNF-$\alpha$-induced MMP-9 activity was reduced by the treatment of saxatilin. These results indicate that transcriptional regulation of MMP-9 is an important mechanism for the tumor suppressive effects of saxatilin in MDAH 2774 human ovarian cancer cells.

• 한국임상수의학회지
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• 제37권5호
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• pp.249-254
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• 2020

Neutrophil extracellular trap (NET) formation is an immune response for the invasion of microbes. The purpose of this study is to examine the effect of zinc on NET formation of porcine peripheral blood polymorphonuclear cells (PMNs). The NET formation of PMNs was measured by fluorescence microplate reader. The production of tumor necrosis factor (TNF)-α in the culture supernatants from zinc-treated peripheral blood mononuclear cells (PBMCs) was measured by enzyme-linked immunosorbent assay (ELISA). Zinc itself did not have no effect on NET formation. However, the NET formation of PMNs was increased by culture supernatants from PBMCs treated with zinc. Also, the NET formation of PMNs was increased by recombinant porcine (rp) TNF-α. The production of TNF-α in PBMCs culture supernatants was shown to increase upon zinc treatments. These NET formations of PMNs increased by either culture supernatant from PBMCs treated with zinc or rpTNF-α were inhibited by treatment of anti-rpTNF-α polyclonal antibody (pAb). These results suggested that zinc has an immunostimulating effect on the NET formation of PMNs, which is mediated by TNF-α released from zinc-treated PBMCs. Therefore, zinc may play an important role for NET formation in the defense of porcine inflammatory diseases.

• Journal of Periodontal and Implant Science
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• 제45권3호
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• pp.101-110
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• 2015

Purpose: Sclerostin, an inhibitor of Wnt/${\beta}$-catenin signaling, exerts negative effects on bone formation and contributes to periodontitis-induced alveolar bone loss. Recent studies have demonstrated that serum sclerostin levels are increased in diabetic patients and that sclerostin expression in alveolar bone is enhanced in a diabetic periodontitis model. However, the molecular mechanism of how sclerostin expression is enhanced in diabetic patients remains elusive. Therefore, in this study, the effect of hyperglycemia on the expression of sclerostin in osteoblast lineage cells was examined. Methods: C2C12 and MLO-Y4 cells were used in this study. In order to examine the effect of hyperglycemia, the glucose concentration in the culture medium was adjusted to a range of levels between 40 and 100 mM. Gene expression levels were examined by quantitative reverse transcription-polymerase chain reaction and Western blot assays. Top-Flash reporter was used to examine the transcriptional activity of the ${\beta}$-catenin/lymphoid enhanced factor/T-cell factor complex. Tumor necrosis factor-alpha ($TNF{\alpha}$) protein levels were examined with the enzyme-linked immunosorbent assay. The effect of reactive oxygen species on sclerostin expression was examined by treating cells with 1 mM $H_2O_2$ or 20 mM N-acetylcysteine. Results: The high glucose treatment increased the mRNA and protein levels of sclerostin. High glucose suppressed Wnt3a-induced Top-Flash reporter activity and the expression levels of osteoblast marker genes. High glucose increased reactive oxygen species production and $TNF{\alpha}$ expression levels. Treatment of cells with $H_2O_2$ also enhanced the expression levels of $TNF{\alpha}$ and sclerostin. In addition, N-acetylcysteine treatment or knockdown of $TNF{\alpha}$ attenuated high glucose-induced sclerostin expression. Conclusions: These results suggest that hyperglycemia increases sclerostin expression via the enhanced production of reactive oxygen species and $TNF{\alpha}$.

• 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.

• Perinatology
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• 제29권4호
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• pp.170-174
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• 2018

Objective: Progesterone is used to prevent recurrent preterm delivery, however the molecular mechanisms of its effect are incompletely understood. The objective of this study was to determine the effect of progesterone on tumor necrosis factor $(TNF)-{\alpha}$-induced matrix metalloproteinase (MMP)-9 activity in human choriodecidual (CD) membranes. Methods: We collected CD membranes from women with uncomplicated term pregnancies who were scheduled for elective cesarean delivery (n=10). CD membranes ($1{\times}1cm$) were incubated in tissue culture media at $37^{\circ}C$. We pre-treated the CD membranes with progesterone (P4), $17{\alpha}$-hydroxyprogesterone caproate (17P), promegestone (R5020), or vehicle (ethanol) for 24 hours. The CD membranes were subsequently treated with $TNF-{\alpha}$ (with continued progesterone treatment) for 48 hours, then media was harvested for measuring MMP-9 activity by zymography and total protein was isolated from CD membrane tissues for MMP-9 expression by western blot analysis. Results: P4, 17P, and R5020 significantly reduced $TNF-{\alpha}$-induced MMP-9 activity in fetal membrane tissue samples (P=0.0078, P=0.0156, and P=0.0391, respectively) by zymography. Western blot analysis also showed decreased expression of MMP-9 in progesterone pretreated groups (P=0.0313). Conclusion: Progesterone reduces $TNF-{\alpha}$-induced MMP-9 activity in human CD membranes. These findings may provide further support for the role of progesterone in preventing preterm birth.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2637-2641
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• 2016

Tumor necrosis factor ($TNF-{\alpha}$), an inflammatory cytokine that plays an important role in the control of cell proliferation, differentiation, and apoptosis, has previously been used in anti-cancer therapy. However, the therapeutic applications of $TNF-{\alpha}$ are largely limited due to its general toxicity and anti-apoptotic influence. To overcome this problem, the present study focused on the effect of active constituents isolated from a medicinal plant on $TNF-{\alpha}$-induced apoptosis in human colon adenocarcinoma (HT-29) cells. Nimbolide from Azadirachta indica was evaluated for cytotoxicity by methyl tetrazolium 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay and phase contrast microscopy. Effects on apoptotic signaling proteins were investigated using Western blot analysis. Nimbolide showed cytotoxicity against HT-29 cells that was significantly different from the control group (p<0.01), a concentration of $10{\mu}M$ significantly inducing cell death (p<0.01). In combination with $TNF-{\alpha}$, nimbolide significantly enhanced-induced cell death. In apoptotic pathway, nimbolide activated c-Jun N-terminal kinase (JNK) phosphorylation, BH3 interacting-domain death agonist (Bid) and up-regulated the death receptor 5 (DR5) level. In the combination group, nimbolide markedly sensitized $TNF-{\alpha}$-induced JNK, Bid, caspase-3 activation and the up-regulation of DR5. Our findings overall indicate that nimbolide may enhance $TNF-{\alpha}$-mediated cellular proliferation inhibition through increasing cell apoptosis of HT-29 cells by up-reglation of DR5 expression via the JNK pathway.

• 대한물리의학회지
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• 제8권4호
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• pp.539-547
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• 2013

PURPOSE: This study examined the effects of exercise of diverse intensities on the expression of TNF-${\alpha}$(tumor necrosis factor-${\alpha}$) in the spinal cord in osteoarthritic rats. METHODS: Over a period of four weeks, the authors applied treadmill exercise programs of diverse intensities to Sprague-Dawley rats, to which intra-articular injection of monosodium iodoacetate(MIA, $3mg/50{\mu}l$, diluted in saline) was applied to the right knee joint to induce osteoarthritis. The four-week exercise program was not carried out with the control group(CG, n=10). Exercise programs of applicable intensities were applied to the low-intensity exercise group(LEG, n=10), moderate-intensity exercise group (MEG, n=10), and high-intensity exercise group(HEG, n=10) over the four weeks. Observations were made of expression of TNF-${\alpha}$ in the spinal cord in osteoarthritic rats using western blot analysis. RESULT: there were significant differences(p<.05) in the comparison of expression of TNF-${\alpha}$ between the four groups involved. The expression of TNF-${\alpha}$ in the spinal cord, the LEG and HEG had more elevated expression significantly than the CG(p<.05). But the MEG had reduced expression significantly than the CG(p<.05). CONCLUSION: These study results suggest that moderate-intensity exercise is effective in inhibition TNF-${\alpha}$ in the spinal cord. They also indicate that in prescribing exercise to treat osteoarthritic patients, exercise of moderate intensity is most suitable to patients' chronic pain, rather than low or high intensity.