• 대한한의학회지
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• 제26권1호
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• pp.85-92
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• 2005

Objective: A number of candidate genes have been in implicated in the pathogenesis of obesity in humans. Tumor necrosis factor-alpha $(TNF-{\alpha})$ is expressed primarily in adipocytes, and elevated levels of this cytokine have been linked to obesity and insulin resistance. Recently, the A allele of a polymorphism at position 308 in the promoter region of $TNF-{\alpha}$ (G-308A) has been shown to increase transcription of the gene in adipocytes. Therefore, we designed this study to test whether obese and non-obese subjects differ in $TNF-{\alpha}$ genotype distribution, and how the genotypes affect anthropometric parameters, including degrees of body mass index (BMI). Methods : The study included 153 obese but otherwise healthy women ($BMI{\geq}kg/m^2$, range 25-54.7, age range 15-40 years) and 82 non-obese healthy women ($BMI, age range 15-40 years). Total fat mass and percent body fat were determined by dual-energy X-ray absorptiometry. Genomic DNA was extracted and used for Ncol restriction fragment length polymorphism (RFLP) based genotyping of $TNF-{\alpha}$. Results: No differences were observed for allelic and genotype frequencies between the obese ($BMI{\geq}25$) and non-obese women. Also, no association of TNF-(l polymorphism was observed with body mass index (BMI) for genotype in obese women. In addition, age, pertent body fat, BMI, and cholesterol levels did not differ by $TNF-{\alpha}$ genotype. However, waist-to­hip ratio (WHR) was significantly lower in subjects with $TNF-{\alpha}$ GA or AA genotype (0.94 0.07 vs. 0.920.03, P<0.005). Conclusion: These results suggest that $TNF-{\alpha}$ promoter polymorphism at position-308 is not a significant factor for BMI, but affects the WHR in obese healthy women from Koreans.

• 대한한방부인과학회지
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• 제21권1호
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• pp.39-54
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• 2008

Purpose: The purpose of this study was to investigate the anti-inflammatory effects of the water extract of Omisodokeum (OMSDE) on peritoneal macrophages, Methods: To verify the anti-inflammatory mechanism of OMSDE, the activation of nuclear $factor-{\kappa}B$ $(NF-{\kappa}B)$ and the phosphorylation of MAPK were examined. Results: The extract of OMSDE suppressed the production of LPS-induced nitric oxide (NO), tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, IL-6 and IL-12 in the macrophages. OMSDE inhibited the degradation of inhibitory ${\kappa}B-{\alpha}$ $(I{\kappa}B-{\alpha})$ and it suppressed the activation of extracellular signal-regulated kinase (ERK 1/2) but didn't inhibit c-Jun N-terminal kinase (JNK) and p38, indicating that OMSDE may inhibit the pro-inflammatory cytokine production process by inhibiting the activation of $NF-{\kappa}B$ and ERK 1/2. Furthermore, OMSDE inhibited the production of interferon $(IFN)-{\beta}$ but didn't inhibit of $IFN-{\alpha}$ in the LPS-stimulated macrophages through the down-regulation of interferon regulatory factor (IRF)-1 and IRF-7. The Oral administration of OMSDE inhibited LPS-induced endotoxin shock and the production of $TNF-{\alpha}$ in serum but didn't inhibit of $IL-1{\beta}$ and IL-6. Conclusion: These results suggest that OMSDE may be effective in the prevention and treatment of inflammatory diseases.

• Restorative Dentistry and Endodontics
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• 제24권1호
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• pp.187-199
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• 1999

Bone remodeling is characterized by the continuing processes of osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Bone metabolism is tightly regulated at the local level by networks of hormones, cytokines, and other factors. In pathological conditions of bone remodeling, including osteoporosis and periodontal diseases, inflammatory cytokines and local mediators are responsible for enhancement of osteoclast resorption and inhibition of repair at the sites of bone resorption. TNF-${\alpha}$ is a pleiotropic hormone with actions on the differentiation, growth, and functional activities of normal and malignant cells from numerous tissues. TNF-${\alpha}$ has been proposed as a local mediator of the control of bone turnover in situations of chronic inflammation, and it has been assumed that the local source of TNF-${\alpha}$ is the monocyte in the adjacent bone marrow or the local circulation. TNF-${\alpha}$ is a potent inducer of bone resorption. TNF-${\alpha}$ is known to induce the activation of apoptotic signaling pathway, which leads to the apoptosis of bone cells. We demonstrated that treatment of murine osteoblastic MC3T3E1 cells with TNF-${\alpha}$ decreases proliferation as well as alkaline phosphatase (ALP) activity in a dose depenent manner. In addition, TNF-${\alpha}$ increases osteoclast-like cell formation in $1{\alpha}$, 25(OH)2D3 or PGE2-treated bone marrow cell culture. When cells were cultured in TNF-${\alpha}$ free ${\alpha}$-MEM, this inhibitory effect of ALP activity was reversible up to 10 ng/ml TNF-${\alpha}$, in contrast, at the 20 ng/ml TNF-${\alpha}$, irreversible. In this concentration, TNF-${\alpha}$ may induce apoptosis in MC3T3E1 cells. In this study, TNF-${\alpha}$ induces apoptosis resulting in chromosomal DNA fragmentation, preceded by JNK/SAPKs and caspase-3 activation. Our present results show that JNK/SAPKs and caspase-3 are activated by TNF-${\alpha}$, suggesting that the JNK/SAPKs and caspase-3 participate in the bone resorption, associated with apoptosis.

• 대한의생명과학회지
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• 제24권3호
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• pp.168-174
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• 2018

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by abdominal pain, rectal bleeding and diarrhea. Gastrodia elata Blume (GE) has been used for the treatment of various diseases including neurodegenerative diseases and inflammatory disease. However, there has been no information on whether GE regulates intestinal inflammation. The aim of this study is to elucidate whether GE can protect against dextran sulfate sodium (DSS)-induced colitis in a mouse model. The colitis mice were induced by drinking water containing 5% DSS for 7 days. Body weight, colon length and clinical score were assessed to determine the effects on colitis. The levels of inflammatory cytokines, tumor necrosis factor $(TNF)-{\alpha}$ and interleukin (IL)-6 in colitis tissue were also measured. The results showed that mice administrated with DSS showed clinical signs including weight loss and reduced colon length. GE inhibited the DSS-induced loss of body weight and shortening of colon and increased Disease activity index score. Additionally, we observed that GE suppressed the levels of $TNF-{\alpha}$ and IL-6 in DSS-treated colon tissues. Collectively, these findings provide experimental evidence that GE might be a useful therapeutic agent for patients with UC.

• 한국임상수의학회지
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• 제25권6호
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• pp.440-446
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• 2008

Glucocorticoids (GCs) are the most widely used immunosuppressive agents, but animals treated with GCs may experience deleterious side effects which limit their use in many clinical conditions. In the present study, we examined whether methylprednisolone sodium succinate (MPSS), a glucocorticoid, modulates circulating leukocyte numbers, phagocytic capacity and oxidative burst activity (OBA) of canine peripheral blood phagocytes, and whether tumor necrosis factor-alpha (TNF-$\alpha$) release is affected by MPSS injection. Neutrophilia and monocytosis were induced by the administration of a high dose of MPSS, which is the recommended protocol for canine patients with acute spinal cord injury. The injection of MPSS decreased the phagocytic capacity of canine PMNs but not PBMCs, and recovered 12 hours (hr) after the completion of MPSS dosing. The OBA of both PMNs and PBMCs was suppressed by MPSS, and restored 24 hr after the completion of dosing. The lipopolysaccharide-induced TNF-α release by PBMCs but not PMNs exposed to MPSS was reduced 12 hr after the completion of dosing, and recovered 48 hr after the completion of dosing. These results suggest that the application of MPSS protocol inhibits the innate immune functions of canine peripheral blood phagocytes for short time relatively.

• Journal of Veterinary Science
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• 제19권6호
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• pp.744-749
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• 2018

Dapsone, an antibiotic, has been used to cure leprosy. It has been reported that dapsone has anti-inflammatory activity in hosts; however, the anti-inflammatory mechanism of dapsone has not been fully elucidated. The present study investigated the anti-inflammatory effects of dapsone on bone marrow cells (BMs), especially upon exposure to lipopolysaccharide (LPS). We treated BMs with LPS and dapsone, and the treated cells underwent cellular activity assay, flow cytometry analysis, cytokine production assessment, and reactive oxygen species assay. LPS distinctly activated BMs with several characteristics including high cellular activity, granulocyte changes, and tumor necrosis factor alpha ($TNF-{\alpha}$) production increases. Interestingly, dapsone modulated the inflammatory cells, including granulocytes in LPS-treated BMs, by inducing cell death. While the percentage of Gr-1 positive cells was 57% in control cells, LPS increased that to 75%, and LPS plus dapsone decreased it to 64%. Furthermore, dapsone decreased the mitochondrial membrane potential of LPS-treated BMs. At a low concentration ($25{\mu}g/mL$), dapsone significantly decreased the production of $TNF-{\alpha}$ in LPS-treated BMs by 54%. This study confirmed that dapsone has anti-inflammatory effects on LPS-mediated inflammation via modulation of the number and function of inflammatory cells, providing new and useful information for clinicians and researchers.

• 생명과학회지
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• 제24권7호
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• pp.721-727
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• 2014

버섯 다당류 ${\beta}$-glucan의 항암 활성을 확인하기 위하여 영지균사체로부터 단백다당류(GLP)를 분리하고 Sarcoma-180 육종암을 이식시킨 마우스에 복강 투여하여 항암활성을 확인하였다. 육종암이 서혜부에 이식된 마우스에 GLP를 20 mg/kg의 농도로 10일간 복강투여 한 후 30일차에 확인한 결과, Sarcoma-180 육종암은 대조군대비 71.4% 억제되었으며, 마우스의 혈청, 종양조직 및 간조직 내의 TNF-${\alpha}$의 농도는 대조군보다 높게 나타났다. 따라서 GLP는 생체 내 TNF-${\alpha}$의 양적증가를 유도하며, 종양괴사 또는 에폽토시스와 연관된 육종암의 생장억제가 확인되었다. 이때 생장이 억제된 육종암 세포의 미세구조를 관찰한 결과, 상대적으로 큰 핵과 세포의 에폽토시스에서 전형적으로 보여지는 염색질 응축이 관찰되었으며, 핵막은 특징적으로 뭉쳐져 불규칙한 모양을 나타내었다. 따라서 영지에서 분리된 GLP는 종양 세포의 에폽토시스를 유도하여 종양의 성장을 억제하는 것으로 여겨진다.

• 생명과학회지
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• 제17권10호
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• pp.1354-1360
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• 2007

국산 미생물 발효차의 폴리페놀 색소성분들인 데아플라빈(TF)과 데아루비긴(TR) 및 EGCG를 macrophage cell line (RAW264.7에 적용하여 nitric oxide 합성 및 사이토카인 생성을 평가하였다. 사이토카인 생성은 TF, TR 및 EGCG를 RAW264.5 cell에 적용하였을 때, $80\;{\mu}g/ml$ 농도에서 대조군과 LPS 촉진 처리에 비하여 nitric oxide 생성은 약 1.5배 증가하였다. IL-6, $TNF-{\alpha}$ 및 GM-CSF는 TF, TR 및 EGCG 농도에 의존적으로 증가하였다. $TNF-{\alpha}$ 생성은 크게 증가하였으며, 이는 TF, TR 및 EGCG가 사이토카인 생성을 통하여 면역증강 효과를 가질 것으로 나타났다 TF, TR 및 EGCG는 총 페놀 함량에 비례하여 항산화능을 나타내었으며, 암세포 증식을 유의적으로 억제하였다. 이들 폴리페놀물질의 억제효과는 그 성분들의 항암촉진작용 및 항산화활성에 의한 것으로 판단된다.

• BMB Reports
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• 제53권12호
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• pp.628-633
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• 2020

WNT11 is a member of the non-canonical Wnt family and plays a crucial role in tumor progression. However, the regulatory mechanisms underlying WNT11 expression are unclear. Tumor necrosis factor-alpha (TNFα) is a major inflammatory cytokine produced in the tumor microenvironment and contributes to processes associated with tumor progression, such as tumor invasion and metastasis. By using site-directed mutagenesis and introducing a serial deletion in the 5'-regulatory region of WNT11, we observed that TNFα activates the early growth response 1 (EGR1)-binding sequence (EBS) in the proximal region of WNT11 and that the transcription factor EGR1 is necessary for the TNFα-induced transcription of WNT11. EGR1 bound directly to the EBSs within the proximal 5'-regulatory region of WNT11 and ectopic expression of EGR1 stimulated WNT11 promoter activity, whereas the knockdown of EGR1 expression by RNA interference reduced TNFα-induced WNT11 expression in T47D breast cancer cells. We also observed that mitogen-activated protein kinases (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase mediated TNFα-induced transcription of WNT11 via EGR1. Our results suggest that EGR1 directly targets WNT11 in response to TNFα stimulation in breast cancer cells.

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