• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.611-620
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• 1997

Objectives : The differentiation of tuberculous effusion from the other causes of exudative pleural effusion remained difficult even with aids of biochemical analyses and pleural biopsy. As the pathophysiology of tuberculous pleural effusion is an enhanced cell mediated immunity, Adenosine deaminase(ADA) and various eytokines including Inteferon-$\gamma$, tumor necrosis factor alpha(TNF-$\alpha$) are considered as useful diagnostic tools in differentiating exudative pleural effusion. The author would like to demonstrate the diagnostic usefulness of TNF-$\alpha$ in the differentiation of exudative pleural effusion, and compared the discriminating ability of TNF-$\alpha$ with ADA. Methods : Pleural fluids obtained from 80 patients (tuberculous : 39, malignant : 31, parapneumonic : 10) with exudate pleural effusions were processed for cell counts and biochemical analysis including ADA and TNF-$\alpha$. Results : Tuberculous pleural fluid showed higher levels of ADA and TNF-$\alpha$, $48.7{\pm}32.7U/L$ and $184.1{\pm}214.2pg/mL$ than that of non-tuberculous effusion $26.0{\pm}41.3U/L$ and $44.1{\pm}114.2pg/mL$, respectively (ADA, TNF-$\alpha$, p < 0.05, p < 0.01). Receiver operating characteristics(ROC) curves were generated for ADA and TNF-$\alpha$ and the best cut-off value for adenosine deaminase and TNF-$\alpha$were considered as 30U/L and 15pg/ml, respectively. Comparing the area under the ROC curves, there was no significant difference between ADA and TNF-$\alpha$. Conclusion : For the differential diagnosis of tuberculous pleural effusion from the other causes of exudative pleural effusions, TNF-$\alpha$ as well as ADA was considered as useful diagnostic method. However adding TNF-$\alpha$ to ADA has no further diagnotic benefit than ADA alone.

• Korean Journal of Medicinal Crop Science
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• v.15 no.1
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• pp.30-37
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• 2007

It is well-known that Korean mistletoe (Viscum album) extract has an immune activity and anticancer effect. In this study, Korean mistletoe extract, M11C (non-lectin components), was used to examine whether this extract might activate human peripheral monocyte to produce tumor necrosis $factor-\alpha$ $(TNF-\alpha)$. To examine the effect of M11C on the production of $TNF-\alpha$ from monocyte, the monocyte were stimulated by the M11C, and then collected the supernatant (M11C stimulated monocyte-conditioned media; MCM). MCM was treated to the $TNF-\alpha$ sensitive L929 cells, and then L929 cytotoxicity was measured by means of MTT. MCM had cytotoxic effect on L929. And the cytotoxic effect of MCM on L929 was almost abolished by $anti-TNF-\alpha$ antibody. These data indicated that MCM contained $TNF-\alpha$, suggesting the $TNF-\alpha$ generation from M11C-stimulated monocyte. This suggestion was confirmed from the data that $TNF-\alpha$ was highly detected in MCM by immunoblotting technique. M11C effect on $TNF-\alpha$ production from monocyte was in the dose and stimulating time dependent manners. Also the effect of M11C on the expression of $TNF-\alpha$ mRNA from monocyte was shown in the dose and stimulating time dependent manners. As a result, Korean mistletoe extract, M11C, could be used for an immunostimulator.

• Journal of Food Hygiene and Safety
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• v.21 no.3
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• pp.181-188
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• 2006

Tumor necrosis factor-alpha $(TNF-{\alpha})$ plays a variety of biological functions such as apoptosis, inflammation and immunity. PTEN also has various cellular function including cell growth, proliferation, migration and differentiation. Thus, possible relationships between two molecules are suggested. $(TNF-{\alpha})$has been known to downregulate PTEN via nuclear factor-kappa $B(NF-{\kappa}B)$ pathway in the human colon cell line, HT-29. However, here we show the opposite finding that $(TNF-{\alpha})$ upregulates PTEN via activation of $NF-{\kappa}B$ in HL-60 cells. $TNF-{\alpha}$ increased PTEN expression at HL-60 cells in a time- and dose-dependent manner, but the response was abolished by disruption of $NF-{\kappa}B$ with p65 anisense oligonucleotide or pyrrolidine dithiocarbamate (PDTC). We found that $TNF-{\alpha}$ activated the $NF-{\kappa}B$ pathways, evidenced by the translocation of p65 to the nucleus in $TNF-{\alpha}-treated$ cells. We conclude that $TNF-{\alpha}$ induces upregulation of PTEN expression through $NF-{\kappa}B$ activation in HL-60 cells.

• Journal of Animal Science and Technology
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• v.47 no.5
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• pp.711-720
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• 2005

In the corpus luteum, TNF$\alpha$ is known to induce functional and structural luteolysis. In addition, it acts as luteotropic agent during the initial and early stage of luteal development. In spite of its importance in corpus luteal development, there is still different opinions for the source cells of TNF$\alpha$ in the corpus luteum. One is the macrophages only, and the other is macrophages are the main source and endothelial cells are the minor source. In this experiment, using the porcine corpora lutea of pregnancy and ovulatory stages, hematoxylin-eosin stain, macrophage and TNF$\alpha$ immunohistochemistry were carried to reveal the sources of TNF$\alpha$. As a result, MAC 387-positive macrophages were present in all the stages of corpora lutea. In the mature corpora lutea of nonpregnant stages, the sites of MAC 387-positive macrophages and those of TNF$\alpha$- positive macrophages were coincided, and the sites of endothelial cells and those of TNF$\alpha$-positive endothelial cells were nearly coincided. But, in the mature CL of pregnant stage, mid- and advanced luteolytic stages of both nonpregnant and pregnant stages, the sites of MAC 387-positive macrophages and those of TNF$\alpha$-positive macrophages were coincided, but not in the endothelial cells. Accordingly, it can be concluded that macrophages are the main source of TNF$\alpha$ in the corpus luteum and endothelial cells are the minor source in the mature and mid-lytic stages, but, in the advanced luteolytic stage, macrophages are the only source of TNF$\alpha$.

• Korean Journal of Microbiology
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• v.51 no.3
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• pp.308-311
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• 2015

Chungkookjang (fermented soybeans) contains diverse peptides. Human breast cancer MDA-MB-231 cells were treated with peptide H derived from Chungkookjang, and $TNF{\alpha}$ expression in the cells was conspicuously repressed, suggesting peptide H's regulation of IL6 since IL6 is induced by $TNF{\alpha}$. The structure of peptide H was different from those of glucocorticoid and dexamethasone, suggesting different mechanisms of $TNF{\alpha}$ expression suppression. Peptide H which reduces $TNF{\alpha}$ expression can be developed as drugs for cancer, rheumatoid arthritis and Crohn's disease, after more investigation.

• YAKHAK HOEJI
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• v.52 no.1
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• pp.37-42
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• 2008

Betulinic acid, a naturally occurring pentacyclic triterpenoid, is found in abundance in the outer bark of white birch (Betula alba). In this study, we investigated if betulinic acid affects cytokine expression from activated macrophage cells. ELISA result showed that stimulation of HL-60 cells with proinflammatory cytokine such as $TNF-{\alpha}$ resulted in MCP-1 release into culture medium. In addition, transcriptional upregulation of MCP-1 in response to $TNF-{\alpha}$ was observed by RT-PCR analysis. However, incubation of HL-60 cells with betulinic acid prior to $TNF-{\alpha}$ treatment abrogated MCP-1 expression in transcription and translational level. Consistent with a number of studies which reported requirement of ERK activation for $TNF-{\alpha}$ expression, Western blot analysis showed that $TNF-{\alpha}-induced$ ERK activation was suppressed by pretreatment of HL-60 cells with betulinic acid. Taken together, our data indicate that betulinic acid exerts its anti-inflammatory effect through inhibition of $TNF-{\alpha}-induced$ ERK activation which is required for the subsequent MCP-1 release.

• Archives of Pharmacal Research
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• v.28 no.11
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• pp.1257-1262
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• 2005

MMP-9 is a metalloproteinase capable of basement membrane degradation in vivo. Expression of MMP-9 can be found in normal conditions such as trophoblasts, osteoclasts, and leukocytes and their precursors. They also occur as well as in pathological conditions, such as the invasive growth of primary tumors, metastasis, angiogenesis, rheumatoid arthritis, and periodontal diseases. MMP-9 upregulation can be highly induced by a wide range of agents. These agents include growth factors, cytokines, cell-cell, and cell-ECM adhesion molecules, and agents altering cell shape. Here, we observed that TNF-$\alpha$ stimulated human monocytic cell line, HL-60 produced MMP-9 in a dose and time dependent manner. Real time PCR results indicated transcriptional upregulation of MMP-9 as early as 3 h post TNF-$\alpha$ stimulation. To investigate the signaling pathway underlined in TNF-$\alpha$ induced MMP-9 expression, three MAP kinase inhibitors were added to cells 1 h prior to TNF-$\alpha$ treatment. The ERK inhibitor completely abolished MMP-9 expression by TNF-$\alpha$. But neither p38 MAP kinase nor JNK inhibitor had an effect on TNF-$\alpha$ induced MMP-9 expression, suggesting that ERK activation is required for the MMP-9 induction by TNF-$\alpha$. Taken together, we found that TNF-$\alpha$ stimulation facilitates ERK activation, which results in the transcriptional upregulation of MMP-9 gene and subsequent MMP-9 production and secretion.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.525-531
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• 2010

Purpose : Expression levels of tumor necrosis factor (TNF)-${\alpha}$ expression on the mucosa of the small intestine is increased in patients with villous atrophy in food protein-induced enterocolitis syndrome (FPIES). TNF-${\alpha}$ has been reported to induce apoptotic cell death in the epithelial cells. We studied the TNF family and TNF-receptor family apoptosis on the duodenal mucosa to investigate their roles in the pathogenesis of FPIES. Methods : Fifteen infants diagnosed as having FPIES using standard oral challenge test and 5 controls were included. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to identify the apoptotic cell death bodies. Immunohistochemical staining of TNF-${\alpha}$, Fas ligand (FasL) for TNF family and TNF-related apoptosis-including ligand (TRAIL) receptor 1 (DR4), TRAIL receptor 2 (DR5), and Fas for TNF-receptor family were performed to determine the apoptotic mechanisms. Results : $TUNEL^+$ was significantly more highly expressed in the duodenal mucosa of FPIES patients than in controls ($P$-0.043). TNF-${\alpha}$ ($P$=0.0001) and DR4 ($P$=0.003) were significantly more highly expressed in FPIES patients than in controls. Expression levels of FasL, Fas, and DR5 were low in both groups and were not significantly different between the 2 groups. Conclusion : These results suggest that FPIES pathogenesis is induced by apoptosis, and that TNF-${\alpha}$ expression and DR4 pathway may have an important role in apoptosis.

• The Journal of Internal Korean Medicine
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• v.25 no.1
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• pp.28-45
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• 2004

Objectives : The main purpose of this study is to evaluate the effect of Injinchunggan-tang on $TNF-{\alpha}$ signal transmission system. Materials and Methods : We analyzed the following with quantitative RT-PCR method; the effect of Injinchunggan-tang on secretion of $TNF-\alpha$ mRNA/protein and stability, the effect on gene revelation that consists of signal transmission system (TRAIL, NIK, A20, TRADD, RAIDD, RIP TNFR-I, TNFR-II, TRAF1, TRAF2, FADD), the one on activation of p38, Erk1/2 MAPK and the rate of nuclear $NF-{\kappa}B/cytosolic\;NF-{\kappa}B$ in HepG2 cell. We also analyzed the inhibitory effect of Injinchunggan-tang on the apoptosis of HepG2 cell that $TNF-{\alpha}$ induces and the $NF-{\kappa}B$ restraint effected by transfection of $I{\kappa}B{\Delta}N$ through tryphan blue exclusion assay. Results : Injinchunggan-tang prohibits revelation of $TNF-{\alpha}$ mRNA in HepG2 cell and the creation of protein. However, it has no effect on the stability of $TNF-{\alpha}$ mRNA. While it did not have any effect on the generation of TRAIL, NIK, A20, TRADD, RAIDD and RIP genes, Injinchunggan-tang reduces the revelation of TNFR-I, TNFR-II, TRAF1, TRAF2 and FADD genes. It has been confirmed that Injinchunggan-tang restraints the revelation of $TNF-{\alpha}$ mRNA that is promoted by ethanol, acetaldehyde, lipopolysaccharide, in proportion to the treatment density and time. It activated $NF-{\kappa}B$ of HepG2 cell and promoted activation of $NF-{\kappa}B$ that is occurred by $TNF-{\alpha}$. It has been observed that the restraint effect against the $TNF-{\alpha}$ inducing apoptosis is lost when it is intercepted the function of $NF-{\kappa}B$ in HepG2 cell. Conclusion: It has been confirmed that Injinchunggan-tang has restraining effect against the revelation of $TNF-{\alpha}$ and mRNA that is constituent element of TNF-a signal transmission system. It also has been revealed that it restraints the activation of p38, Erk1/2 by $TNF-{\alpha}$. Through this prohibiting effect, it is inferred that it restraints signal transmission among various cells that are related to inflammation reaction. Meanwhile, Injinchunggan-tang protects liver cell from apoptosis that is caused by $TNF-{\alpha}$, by maintaining the activating function for $NF-{\kappa}B$.

• Journal of Chest Surgery
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• v.34 no.2
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• pp.138-147
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• 2001

배경: 폐암발생에 EGF의 자가 분비는 암의 성장과정에 직, 간접적인 영향을 주고 있으며, TNF-$\alpha$는 면역 반응의 급성체로서 폐암의 발생을 억제하고 이미 발생한 폐암종의 치료에도 이용되고 있는 실정이다. 폐암 조직과 혈장에서 epidermal growth factor(EGF)와 tumor necrosis factor-$\alpha$(TNF-$\alpha$)를 면역 방사선 분석법을 이용하여 정량분석 하여 발현 정도를 분석해보고자 하였다. 대상 및 방법: 폐암환자 20례와 양성종양 및 육아종 환자 4례에 대해서 AJCCS에 의한 조직학적 분류와 TNM 분류에 따라 구분하여 절제수술을 받은 환자를 대상으로 수술전 혈액을 채취하고 수술직후 적출한 표본을 암이 없는 건강하다고 판단되는 대조조직과 폐암조직에서 일정량의 조직을 절취하여 액화질소 내에 실험시까지 급속 냉동보관 하였다. 수술후 혈액을 재 채취하여 혈장을 분리하여 냉동고에 검사시까지 보관하였다. EGF의 정량은 Human Epidermal Growth Factor kit(Amersham Phamacia Biotech, England)를 사용하였으며, TNF-$\alpha$ 정량은 TNF-$\alpha$ IRMA kit(Biosouce, Belgium)을 사용하여 IRMA 방법으로 각각 정량분석하여 표현유무를 연구한 결과 다음과 같은 결론을 얻었다. 결과: 1. 대조조직, 양성종양 및 육아종과 폐암 수술전후의 조직과 혈청 모두에서 EGF와 TNF-$\alpha$가 발현되었다. 2. EGF와 TNF-$\alpha$의 농도는 대조조직과 양성종양(0.11$\pm$0.06 ng/ml, 20,3$\pm$9.08 pg/ml)에 비하여 폐암조직(0.13$\pm$0.05 ng/ml, 34.34$\pm$47.74pg/ml)에서 유의하게 높은 농도가 발현되고 있었다. 3. 폐암중 선암조직에서 특히 TNF-$\alpha$(80.92$\pm$104.08 ng/ml)의 발현이 강하게 나타났다. 4. 혈청내의 EGF와 TNF-$\alpha$의 발현되는 양이 조직내의 양보다도 높았다. EGF는 5.7배정도 TNF는 1.3배정도 강하게 표현되었다. 5. 폐암의 조직학적 종류에 따라서 EGF는 거의 차이가 없었으나 TNF-$\alpha$ 정량치에는 차이가 있었다. 6. TNM stage가 진행함에 따라 EGF는 농도가 증가하였고 TNF-$\alpha$는 오히려 감소하는 반대되는 교차현상이 있었다. 7. 수술직후 EGF는 증가하였으나 TNF-$\alpha$는 오히려 감소하였다. 결론: 결론적으로 저자는 암조직과 대조조직간에 EGF와 TNF-$\alpha$의 표현량의 차이가 있음을 관찰하였으며 또한 조직과 혈청사이에도 표현량에 차이가 있으며 조직보다도 오히려 혈청내의 농도가 높다는 사실을 관찰하였다. EFG와 TNF-$\alpha$는 정상조직이나 양성조직과 폐암조직 모두에서 분비작용되는 cytokines으로 세포기능에 따라 다양하게 표현이 되며 계속적인 연구로서 밝혀야만 할 과제라고 판단된다.