• BMB Reports
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• 제42권6호
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• pp.338-343
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• 2009

The Wnt/$\beta$-catenin signaling pathway alters adipocyte differentiation by inhibiting adipogenic gene expression. $\beta$-catenin plays a central role in the Wnt/$\beta$-catenin signaling pathway. In this study, we revealed that tumour necrosis factor-$\alpha$ (TNF-$\alpha$), a potential negative regulator of adipocyte differentiation, inhibits porcine adipogenesis through activation of the Wnt/$\beta$-catenin signaling pathway. Under the optimal concentration of TNF-$\alpha$, the intracellular $\beta$-catenin protein was stabilized. Thus, the intracellular lipid accumulation of porcine preadipocyte was suppressed and the expression of important adipocyte marker genes, including peroxisome proliferator-activated receptor-$\gamma$ (PPAR$\gamma$) and CCAAT/enhancer binding protein-$\alpha$ (C/EBP$\alpha$), were inhibited. However, a loss of $\beta$-catenin in porcine preadipocytes enhanced the adipogenic differentiation and attenuated TNF-$\alpha$ induced anti-adipogenesis. Taken together, this study indicated that TNF-$\alpha$ inhibits adipogenesis through stabilization of $\beta$-catenin protein in porcine preadipocytes.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.125.2-126
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• 2003

Human tumor necrosis factor-alpha (TNFa) is a key pro-inflammatory cytokine produced by activated monocytes and macrophage as a part of the self-defence machinery. TNF-a converting enzyme (TACE) is the metalloproteinase that processes the membrane bound precursor of TNFa to the soluble component. (omitted)

• Clinical and Experimental Pediatrics
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• 제57권10호
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• pp.440-444
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• 2014

Purpose: Febrile seizures are induced by fever and are the most common type of seizures in children. Although numerous studies have been performed on febrile seizures, their pathophysiology remains unclear. Recent studies have shown that cytokines may play a role in the pathogenesis of febrile seizures. The present study was conducted to identify potential links between serum interleukin-1beta (IL-$1{\beta}$), tumor necrosis factor-alpha (TNF-${\alpha}$), and febrile seizures. Methods: Ninety-two patients with simple or complex febrile seizures (46 patients per seizure type), and 46 controls with comparable age, sex, and severity of temperature were enrolled. Results: The median concentrations of serum IL-$1{\beta}$ in the simple, complex febrile seizure, and control groups were 0.05, 0.1, and 0.67 pg/mL, respectively (P=0.001). Moreover, the median concentrations of TNF-${\alpha}$ in the simple, complex febrile seizure, and control groups were 2.5, 1, and 61.5 pg/mL, respectively (P=0.001). Furthermore, there were significant differences between the case groups in serum IL-$1{\beta}$ and TNF-${\alpha}$ levels (P<0.05). Conclusion: Unlike previous studies, our study does not support the hypothesis that increased IL-$1{\beta}$ and TNF-${\alpha}$ production is involved in the pathogenesis of febrile seizures.

• Pediatric Infection and Vaccine
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• 제21권3호
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• pp.225-230
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• 2014

최근 가와사키병에서 tumor necrosis factor-alpha(TNF-alpha) blocker인 infliximab 단일 정주 요법이 불응성 가와사키병 환자들에게 유용한 치료제로 여겨지고 있다. 장기적인 TNF-alpha blocker 사용이 기회감염의 위험을 증가시킬 수 있지만, 가와사키병 환자들에게 infliximab 사용이 심각한 부작용을 초래하지 않으며 안전하게 사용된 증례들이 보고된 바 있다. 불응성 가와사키병을 앓고 있는 5개월 된 영아에서 infliximab (5 mg/kg) 단일 정주 요법을 사용하였고 가와사키 증상이 호전되었으나 infliximab 치료 후 Acinetobacter lwoffii에 의한 패혈증이 발생하였다. 그래서 저자들은 불응성 가와사키병을 앓은 영아에서 infliximab 치료 후 발생한 패혈증의 첫 사례를 보고하며 infliximab 치료 선택에 있어 기회 감염의 위험성에 대해 고려할 것을 당부하는 바이다.

• Clinical and Experimental Pediatrics
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• 제48권8호
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• pp.871-876
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• 2005

목 적 : 한국 소아 1형 당뇨병에서 TNF promoter -857T/C와 -1031C/T 및 $LT-{\alpha}$ 유전자 다형성과 질병감수성과의 관련성을 평가하고자 하였다. 방 법 : 1형 당뇨병으로 진단 받은 소아 49명(여아 29명, 남아 20명)과 정상 대조군 94명의 혈액을 채취하여 DNA를 추출하였다. 추출한 DNA에 대하여 allele-specific PCR법을 이용하여 TNF promotor -1031C/T 다형성을, PCR-RFLP법을 이용하여 TNF promotor -857T/C, $LT-{\alpha}$ 유전자 다형성을 분석하였다. 결 과 : 환자군과 대조군 사이에서 TNF promoter -857T/C, -1031C/T 다형성의 분포는 차이가 없었다. 환자들의 임상적 특징에 따라 아군(subgroup)으로 분류하였을 때, 진단 시 당뇨병성 케톤산혈증으로 발현한 환자들에서 TNF promoter -1031C/T 다형성의 TT 유전자형의 빈도가 당뇨병성 케톤산혈증으로 발현하지 않은 환자들과 비교하여 유의하게 낮았다(P<0.05). 다른 임상적 특성들과 이들 유전자 다형성 사이에는 관련성이 없었다. 또 환자와 대조군 사이에 $LT-{\alpha}$ 유전자 다형성의 분포는 차이가 없었으며, 임상적 특성과의 관련성도 없었다. 결 론 : 이 연구를 통하여 TNF promoter -857T/C, $LT-{\alpha}$ 유전자 다형성이 한국 소아에서 1형 당뇨병의 질병감수성과 관련이 없음을 알 수 있었다. 그러나 TNF promoter -1031C/T 다형성은 당뇨병성 케톤산혈증과 같은 1형 당뇨병의 특정 임상양상에 영향을 미칠 수 있는 유전적 인자로 생각된다.

• 대한한방내과학회지
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• 제27권4호
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• pp.864-878
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• 2006

목적 : 인삼은 다양한 생물학적 작용이 있다. 그 중 항염증작용과 관련하여 염증성 사이토카인 분비 및 저산소 유도인자-1${\alpha}$ 활성화 조절 효과를 살펴보고자 한다. 방법 : phorbol myristate acetate (PMA)+A23187에 유도된 세포에서 염증성 cytokines 분비의 변화와 인간의 mast cell인 HMC-1 cells에서 hypoxia-inducible factor-1 (HIF-1)${\alpha}$의 작용을 관찰하였다. 결과 : PMA+A23187은 대조군과 비교해서 interleukin $(IL)-1{\beta}$, IL-6와 tumor necrosis factor $(TNF)-{\alpha}$의 분비를 증가시킨다. 또한 증가된 cytokines IL-1, IL-6, $TNF-{\alpha}$가 인삼의 처리에 의해 두드러지게 억제하는 것을 확인하였다. 인삼(5 ${\mu}g/ml$)은 $IL-1{\beta}$, IL-6, $TNF-{\alpha}$의 분비를 약 105.1${\pm}$9.7%, 95${\pm}$9.4%, 29.7${\pm}$4.5%,(P<0.05)로 최대로 억제하였고, PMA+A23187에 유도된 vascular endothelial growth factor (VEGF)와 granulocyte macrophage-colony stimulating factor (GM-CSF)의 분비를 41.3%와 75.7%로 각각 억제하였다. 그리고 저자는 인삼이 PMA+A23187로 유도된 HIF-1${\alpha}$ 발현과 HIF-1에 대해 DNA binding activity를 억제하고 있음을 관찰하였다. 결론 : 인삼이 HIF-1에서 염증반응을 억제함을 나타내고, 이는 인삼이 염증성 질환을 치료하는데 유익한 효과가 있음을 의미한다.

• Natural Product Sciences
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• 제25권3호
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• pp.215-221
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• 2019

Inflammation is the crucial biological process of immune system which acts as body's defense and protective response against the injuries or infection. However, the systemic inflammation devotes the adverse effects such as multiple inflammation associated diseases. One of the best ways to treat this entity is by blocking the tumor necrosis factor alpha ($TNF-{\alpha}$) and TNF-related apoptosis-inducing ligand (TRAIL) to avoid the proinflammation cytokines production. Thus, this study aims to evaluate the potency of Sambucus bioactive compounds as anti-inflammation through in silico approach. In order to assess that, molecular docking was performed to evaluate the interaction properties between the $TNF-{\alpha}$ or TRAIL with the ligands. The 2D structure of ligands were retrieved online via PubChem and the 3D protein modeling was done by using SWISS Model. The prediction results of the study showed that caffeic acid (-6.4 kcal/mol) and homovanillic acid (-6.6 kcal/mol) have the greatest binding affinity against the $TNF-{\alpha}$ and TRAIL respectively. This evidence suggests that caffeic acid and homovanillic acid may potent as anti-inflammatory agent against the inflammation associated diseases. Finally, this study needs further examination and evaluation to validate the potency of Sambucus bioactive compounds.

• Tuberculosis and Respiratory Diseases
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• 제80권1호
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• pp.60-68
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• 2017

Background: Mucus hypersecretion from airway epithelium is a characteristic feature of airway inflammatory diseases. Tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) regulates mucin synthesis. Glucocorticoids including mometasone fuorate (MF) have been used to attenuate airway inflammation. However, effects of MF on mucin production have not been reported. Methods: Effects of MF and budesonide (BUD) on the phorbol-12-myristate-13-acetate (PMA)-induction of mucin and TNF-${\alpha}$ in human airway epithelial cells (NCI-H292) were investigated in the present study. Confluent NCI-H292 cells were pretreated with PMA (200 nM) for 2 hours. Subsequently, the cells were stimulated with MF (1-500 ng/mL) or BUD (21.5 ng/mL) for 8 hours. Dexamethasone ($1{\mu}g/mL$) was used as the positive control. Real-time polymerase chain reaction was used to determine MUC2 and MUC5AC mRNA levels. The level of total mucin, MUC2, MUC5AC, and TNF-${\alpha}$ in culture supernatants were measured using enzyme-linked immunosorbent assay. Results: MF and BUD significantly suppressed MUC2 and MUC5AC gene expression in PMA-stimulated NCI-H292 cells. The inhibitory effects of the two steroid drugs were also observed in the production of total mucin, MUC2 and MUC5AC proteins, and TNF-${\alpha}$. Conclusion: Our findings demonstrated that MF and BUD attenuated mucin and TNF-${\alpha}$ production in PMA-induced human airway epithelial cells.

• 한국축산식품학회지
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• 제34권1호
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• pp.88-98
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• 2014

Total spleen lymphocytes, lymphocyte proliferation, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interleukin-10 (IL-10) in spleen lymphocyte culture were studied in malnourished Wistar rats fed with goat milk yoghurt. Malnourished rats were created by using standard feed restriction as much as 50% of normal rats for 21 d. Goat milk yoghurt containing three types of microorganism e.g., Lactobacillus acidophilus, Sterptococcus thermophilus and Bifidobacterium longum derived from Lacto-B culture in powder form. After 21 d, the rats continued to receive restricted feeding and supplemented with goat milk yoghurt for 7 d. Total splenocytes were counted by hemocytometer. Splenocytes proliferation was expressed as stimulation index, whereas the TNF-${\alpha}$ and IL-10 of spleen lymphocyte culture were measured by ELISA technique. The total number of splenocytes and stimulation index of splenocytes in moderate malnourished and normal rats supplemented with goat milk yoghurt was not significantly different. The level of TNF-${\alpha}$ in the rat supplemented with goat milk yoghurt was lower (p<0.05) than the control group, whereas the level of IL-10 in the rat supplemented with goat milk yoghurt was higher (p<0.05) than the control group. In conclusion, goat milk yoghurt supplementation in malnourished rats could decrease TNF-${\alpha}$ as a representation of the pro-inflammatory cytokine, while it increases IL-10 as a representation of the anti-inflammatory cytokine.

• Journal of Ginseng Research
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• 제24권2호
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• pp.79-82
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• 2000

사포닌은 인삼의 약리작용을 매개하는 인삼의 주요 성분이다. 인삼의 뿌리는 여러 가지 독소에 의하여 유발되는 독성에 대한 보호작용이 있는 것으로 알려지고 있다. 본 연구에서는 세균독소(lipopolysaccharides)에 의하여 유도되는 종양괴사인자 생성에 미치는 인삼 사포닌의 영향을 살펴보았다. 독소를 투여한 생쥐의 혈청중 종양괴사인자의 농도는 상승하는데, 인삼 사포닌 50 mg/kg을 독소와 함께 복강으로 투여한 경우는 독소만 투여하였을 때에 비하여 혈정 중 종양괴사인자의 농도가 현저히 낮았다. 이러한 인삼 사포닌의 효과는 사포닌의 용량, 투여방법과 투여시간에 영향을 받았는데, 사포닌을 경구로 투여하거나 독소를 주사한 후에 투여하였을 때에는 종양괴사인자 농도에 유의성 있는 차이를 나타내지 않았다. 이러한 결과는 인삼이 간 손상에 대한 보호작용이 있을 가능성을 시사하였고, 사포닌이 이러한 인삼의 보호효과를 매개하는 활성 성분임을 의미한다.