• Environmental Analysis Health and Toxicology
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• v.28
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• pp.12.1-12.5
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• 2013

Objectives The role of genetic polymorphisms of tumor necrosis factor-alpha (TNF-${\alpha}$) for lung cancer development was evaluated. Methods Genotypes of the TNF-${\alpha}$ polymorphisms, -1210C>T, -487A>G, -417A>G, IVS1+123G>A, and IVS3+51A>G, were determined in 616 lung cancer cases and 616 lung cancer-free controls. Results After adjusting for body mass index and smoking, each TNF-${\alpha}$ genotype or haplotype composed of five TNF-${\alpha}$ single nucleotide polymorphisms did not show an association with lung cancer risk (p>0.05). The statistical power was found to be 88.4%, 89.3%, 93.3%, 69.7%, and 93.9% for 1210C>T, -487A>G, -417A>G, IVS1+123G>A, and IVS3+51A>G, respectively. Furthermore, the effects of each SNP or haplotype on lung cancer risk were not found to be different according to the cell type of lung cancer (p>0.05). In the repeated analysis with only subjects without other diseases related to inflammation, there was also no association between polymorphisms or haplotypes of the TNF-${\alpha}$ gene and lung cancer risk (p>0.05). Conclusions This study found no association between common variants of the TNF-${\alpha}$ gene and lung cancer risk.

• Clinical and Experimental Reproductive Medicine
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• v.36 no.1
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• pp.35-43
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• 2009

Objectives: Seminal concentration of tumor necrosis factor-alpha (TNF-${\alpha}$) relevant to sperm nuclear DNA integrity has not been studied. The present study aimed to evaluate seminal concentration of TNF-${\alpha}$ in correlation with sperm parameters and nuclear DNA integrity in asymptomatic healthy donors. Methods: Semen samples were obtained by masturbation from forty-five healthy donors. Results: Sperm quality was assessed by computer-assisted semen analysis and nuclear DNA integrity measured by the TUNEL assay in raw semen. TNF-${\alpha}$ concentrations were measured by ELISA in frozen-thawed seminal plasmas. Sperm DNA fragmentation rates were ranged between 1.9% and 53.0% (mean${\pm}$SD, 12.4${\pm}$9.6%). Univariate analysis revealed that DNA fragmentation rate was not associated with sperm concentration or motility but had a correlation with linearity negatively (r=-0.325, p=0.03) and age positively (r=0.484, p=0.001). The mean seminal concentration of TNF-${\alpha}$ was 4.9 pg/mL with a range from 1.1 to 22.6 pg/mL. The TNF-${\alpha}$ concentration had no correlation with clinically relevant parameters of sperm quality or nuclear DNA fragmentation rate. Conclusion: Our results indicate that sperm nuclear DNA fragmentation may be not associated with seminal TNF-${\alpha}$ level or sperm quality in asymptomatic healthy donors.

• Journal of Chest Surgery
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• v.33 no.1
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• pp.1-6
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• 2000

Background: TNF-$\alpha$ plays a major role in producing left ventricular dysfunction cardio-myopathy pulmonary edema and inhibits the compensatory mechanism of congestive heart failure. IL-6 is an acute reactant of immune reaction and also known to control immune reaction but its function in the myocyte was not clearly investigated. Author's performed this experiment to investigate the contents of TNF-$\alpha$ and IL-6 on the assumption that TNF-$\alpha$ and IL-6 may reside in nonfailing heart that has gone cardiac surgery and play some role in cardiac function. Material and Method : Right auricular tissues were sampled from 12 patients who had undergone total corrective surgery for both congenital and acquired heart diseases from January 1998 to June 1998 in Kosin Universcfy Gospel hospital. The quantitive analysis of TNF-$\alpha$ and IL-6 were assessed by ELISA method in right auricular tissue. Hemodynamic values about the pressure of ventricle atrium aorta pulmonary artery and cardiac index pulmonary and systemic vascular resistance and cardiac output were measured by echocardiography and cardiac catheterization and biochemical analyses of LDH & AST were done before operation. statistical analysis was by Paired Student t-test. Patients were divided into children(under 15 years olds) and adults groups and the data was compared beween two groups. Conclusion: Mild pulmonary hypertension and increased pulmonary vascular resistance were existed in both group. The contents of tissue TNF-$\alpha$ IL-6 in each group were independent of each data.

• Toxicological Research
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• v.13 no.3
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• pp.203-208
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• 1997

The antigenic potential of M3S tumor necrosis factor-$\alpha$(M3S TNF), which is a mutated form of TNF(TNF mutein) designed to reduce adverse effects of wild type human TNF, was investigated in the present study. The antigenicity of M3S TNF was examined by conducting active systemic anaphylaxis (ASA) test in guinea pigs, heterologous(mouse-rat) passive cutaneous anaphylaxis(PCA) test and passive hemagglutination(PHA) test. The experimental animals were divided into low, medium, high and the highest dose groups and the groups with or without immunoadjuvant, sensitized according to the appropriate schedule and challenged. In ASA test, when challenged with 120 $\mu\textrm{g}$ /animal, moderate to severe positive anaphylactic responses were observed in groups sensitized with 12 $\mu\textrm{g}$ /animal, 120 $\mu\textrm{g}$ /animal and 120 $\mu\textrm{g}$ /animal+Freund's complete adjuvant. In PCA test, positive responses were observed in the group sensitized with the highest dose emulsified with an alum(12 $\mu\textrm{g}$ /animal+alum). In PHA test, positive responses were observed in the group sensitized with 3 $\mu\textrm{g}$ /animal emulsified with an alum. All the other groups in each experiment showed negative responses. Based on these results, M3S TNF is considered to have some antigenic potential.

• Journal of Life Science
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• v.29 no.11
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• pp.1251-1257
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• 2019

Peptidoglycan (PG) is found in atheromatous lesions of arteries, where monocytes/macrophages express inflammatory cytokines, including tumor necrosis factor-alpha ($TNF-{\alpha}$). This study investigated the effects of PG on $TNF-{\alpha}$ expression and examined possible cellular factors involved in $TNF-{\alpha}$ upregulation. The overall aim was to identify the molecular mechanisms underlying inflammatory responses to bacterial pathogen-associated molecular patterns in the artery. Exposure of human THP-1 monocytic cells to PG enhanced the secretion of $TNF-{\alpha}$ and induced its gene transcription. Inhibition of TLR-2/4 with OxPAPC significantly inhibited $TNF-{\alpha}$ gene expression, whereas inhibition of LPS by polymyxin B did not. The PG-induced expression of $TNF-{\alpha}$ was also significantly suppressed by pharmacological inhibitors that modulate activities of cellular signaling molecules; for example, U0126 (an ERK inhibitor), SB202190 (a p38 MAPK inhibitor), and SP6001250 (a JNK inhibitor) significantly attenuated PG-induced transcription of $TNF-{\alpha}$ and secretion of its gene product. $TNF-{\alpha}$ expression was also inhibited by rapamycin (an mTOR inhibitor), LY294002 (a PI3K inhibitor), and Akt inhibitor IV (an Akt inhibitor). ROS-regulating compounds, like NAC and DPI, also significantly attenuated $TNF{\alpha}$ expression induced by PG. These results suggest that PG induces $TNF-{\alpha}$ expression in monocytes/macrophages by multiple molecules, including TLR-2, PI3K, Akt, mTOR, MAPKs, and ROS.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2001.08a
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• pp.45-47
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• 2001

생쥐 착상전 초기배아에서 insulin과 tumor necrosis factor $\alpha$ (TNF$\alpha$)에 의한 배아의 형태 발생, 세포증식, apoptosis 및 MAPK활성의 변화를 조사하였다. Insulin에 의해 형태발생 및 포배당 세포수가 증가되었으며 TNF $\alpha$ 처리시 유의하게 감소하였다. TNT$\alpha$ 전처리시 insulin에 의한 발생 및 세포수 증가 촉진효과가 상쇄되었으며 TNF$\alpha$는 배아내 caspase-3의 활성을 증가시켰다. Insulin은 단시간내에 포배에서 mitogen activated protein kinase (MAPK or Erk1/2)의 활성을 증가시켰다. TNF$\alpha$는 포배내 MAPK의 활성을 감소시켰다. Insulin 처리 전 TNF $\alpha$를 전처리한 경우 insulin에 의한 MAPK 활성의 증가가 상쇄되었다. 배발생을 촉진하는 인슐린 신호전달 과정은 MAPK cascade를 경유하며 TNF $\alpha$를 경유한 신호전달과 Crosstalk이 존재하는 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7831-7834
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• 2014

Objective: To explore the influence of different ways of blood transfusion on the expression levels of interleukins (IL) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) inperi-operative patients with esophageal cancer. Materials and Methods: A total of 80 patients with esophageal cancer who underwent radical operations were selected as study patients and randomly divided into an observation group (treated with autologous blood transfusion) and control group (with homologous blood transfusion). Changes of intra-operative indexes and peri-operative blood indexes, from hemoglobin (Hb) and hematocrit value (Hct), to levels of inflammatory factors like interleukins-6 (IL-6), IL-8, IL-10 and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) were compared. Results: Operations for patients in both groups were successfully conducted, and no significant differences in mean surgical duration and intra-operative hemorrhage volume, fluid infusion volume and blood transfusion volume were detected (p>0.05). Compared with values before surgery, Hb and Hct levels decreased significantly while white blood cell count (WBC) increased 1, 5 and 7 d after operation (p<0.05, p<0.01). In addition, WBC was apparently higher in observation group than in control group 5 and 7 d after operation (p<0.01). Compared with before surgery, in the observation group, levels of IL-6, IL-8 and IL-10 had no significant differences after operation (P>0.05), but TNF-${\alpha}$ level increased y (p<0.01), whereas in control group, IL-6 level had no significant difference (p>0.05), IL-8 level decreased obviously (p<0.05), IL-10 level increased markedly first and then decreased gradually as time passed but its level remained elevated (p<0.01), and TNF-${\alpha}$ level increased first and then decreased, and there was no significant difference 7 d after operation (p>0.05). Conclusions: Decreased IL-8 and increased IL-10 levels are two important reasons for immunosuppression after homologous blood transfusion, whereas autologous blood transfusion can alleviate this while increasing the TNF-${\alpha}$ level, which also has potential to improve anti-tumor immunity in the human body.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.4
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• pp.292-296
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• 2004

The recombinant soluble human tumor necrosis factor-alpha (hTNF-$\alpha$) was expressed in a yeast Saccharomyces cerevisiae and its cytotoxicity was evaluated. A cDNA encoding hTNF-$\alpha$ was placed under the control of two different promoters: a glyceraldehyde-3-phosphate dehydrogenase (GPD) promoter and a yeast hybrid ADH2-GPD promoter, consisting of alcohol dehydrogenase II (ADH2) and the GPD promoter. A Northern blot analysis revealed that, although variation in the expression level of hTNF-$\alpha$ existed among transformants, the higher expression was obtained with the GPD promoter. Expressed hTNF-$\alpha$ protein (rhTNF-$\alpha$) was successfully secreted into the culture medium, producing 2.5 mg per liter of culture filtrate, with no changes in cell growth. The bioassay for observing the cytotoxicity to the murine L929 fibroblast cell line, with serial dilution of rhTNF-$\alpha$, indicated that the secreted rhTNF-$\alpha$ was bioactive and its dose-response was improved eight to ten times over that of the E. coli-derived rhTNF-$\alpha$.

• Food Science of Animal Resources
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• v.21 no.4
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• pp.374-382
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• 2001

Lactoferrin(Lf) has the function of modulation in the host defense systems, including cytokine production and immune responses. We have tested the effect of Lf and Lf ydrolysates(Lf-H) on the productions of tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) and nitric oxide(NO) in macrophage cells. Lf from Korean native cattle(K-Lf) and hydrolyzed K-Lf(K-Lf-H) increased the production of TNF-${\alpha}$ in RAW264.7 cells with dose-dependency. Bovine Lf(B-Lf), human Lf(H-Lf), and its hydrolysates did not induce either TNF-${\alpha}$ production or NO production. On the other hand those didn\`t affect on the production of TNF-${\alpha}$ in lipopolysaccharide(LPS)-stimulated RAW264.7 cells. K-Lf induced the production of NO similar to its role on the TNF-${\alpha}$ production.

• The Korean Journal of Pharmacology
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• v.31 no.3
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• pp.323-331
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• 1995

Monocyte/macrophage infiltration is the well known initial features associated with the development of glomerular disease including non-immune mediated nephropathy. Tumor necrosis factor ${\alpha}(TNF{\alpha})$, a cytokine produced primarily by monocyte/macrophage, exhibits similar effects as observed at the initial stages and during the progression of glomerular injury. Because the mesangial cells are target cells for glomerular injury, the present study examined the effect of $TNF{\alpha}$ on glomerular mesangial cell membrane lipid peroxidation as an index of cytotoxicity attributing to $TNF{\alpha}$. Primary culture of rat mesangial cell was established by incubation of glomeruli isolated from male Sprague-Dawley rat kidneys utilizing a standard sieving method. The levels of lipid peroxides in the mesangial cells were quantitated by malondialdehyde- thiobarbituric acid adduct formation. During an 8 hour incubation at $37^{\circ}C$, $TNF{\alpha}$ at 10 to 10,000 units/ml increased the levels of lipid peroxides dose dependently. Western blot analysis demonstrated that a short thermal stress induced heat shock response and the synthesis of heat shock protein 70(hsp70) in this mesangial cells. Further, this induction of hsp 70 prevented increase of lipid peroxides in the mesangial cells exposed to $TNF{\alpha}$. These data suggest that $TNF{\alpha}-induced$ lipid peroxidation in the mesangial cells may have pathophysiological relevance to glomerular injury and prior induction of heat shock response may play a role in the cellular resistance against $TNF{\alpha}-induced$ glomerular injury.