• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3381-3384
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• 2016

Background: Hepatitis B virus (HBV) is a key factor for hepatocellular carcinoma (HCC). About 350 million people are affected by chronic infection which is related to the rapid development of liver diseases as well as hepatitis, cirrhosis and hepatocellular carcinoma. Expression of tumor necrosis factor alpha (TNF-${\alpha}$) in the liver demonstrates a major genetic polymorphism which is involved in resistance or susceptibility to chronic HBV infection. Materials and Methods: In this study, two populations were studied by the sequence specific primer-polymerase chain reaction (SSP-PCR) method: HBV cases (n=409), who were HBS-Ag+, and healthy controls (n=483). Results: The results shown that the frequency of TNF-${\alpha}$ -308 G/G genotype in healthy controls (47.2%) was significantly higher than in HBV infected patients (28%) (CI = 1.29-2.61, OR = 1.83, P = 0.0004). Also TNF-${\alpha}$ -308 A/A and A/G genotype frequencies in the healthy controls were 4.6% and 48.2% and in patient group were 19.5% and 52.5% (CI = 2.23-7.12, p: 0.0001, OR: 3.94) respectively. Conclusions: We found that among Iranian people TNF-${\alpha}$ -308A allele not only has the highest genotype frequency but also it has the highest frequency in the world population. In addition, TNF-${\alpha}$-308 G/G polymorphism was associated with HBV resistance, whereas TNF-${\alpha}$-308A (A/A or A/G) polymorphism appeared to associated with chronic HBV infection. These data suggested that among the Iranian population, the -308 G/G polymorphism of TNF-${\alpha}$ gene promoter region has the potential to influence the susceptibility to HBV infection and it may be responsible for viral antigen clearance.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7141-7148
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• 2014

Background: Oral squamous cell carcinoma (OSCC) is an important malignancy throughout the world; early detection is an important criterion for achieving high cure rate. Out of the many reported markers for OSCC, this study validated the efficacy of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in differentially diagnosing premalignant oral lesions and OSCC. Also, the study aimed to correlate the levels of salivary and serum TNF-${\alpha}$ with clinicopathologic factors. Materials and Methods: A prospective experimental laboratory study was designed. Serum and salivary samples from 100 subjects in each group of healthy control, premalignant disease (PMD) and OSCC were collected for the study following appropriate exclusion and inclusion criteria. Serum and salivary level of TNF-${\alpha}$ was analysed by enzyme linked immunosorbent assay. The data obtained were subjected to appropriate statistical analysis. Results: Increased level of both serum and salivary TNF-${\alpha}$ was observed in OSCC subjects compared to healthy control and PMD group. Receiver operator characteristic curve analysis and area under curve values showed high specificity and sensitivity for salivary TNF-${\alpha}$ in differentiating OSCC from PMD and healthy controls. There was significant increase in TNF-${\alpha}$ level in moderately and poorly differentiated lesion compared to well differentiated lesion and in stage IV of clinical stage. A positive correlation was observed only with histological grading of OSCC and TNF-${\alpha}$. Conclusions: Salivary TNF-${\alpha}$ is proved to be superior for detecting OSCC. Increase in TNF-${\alpha}$ with histological grading and clinical staging suggests a role in prognosis.

• 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.

• International Journal of Oral Biology
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• v.35 no.2
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• pp.43-49
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• 2010

Enterococcus faecalis, a gram-positive bacterium, has been implicated in endodontic infections, particularly in chronic apical periodontitis. Proinflammatory cytokines, including tumor necrosis factor-$\alpha$ (TNF-$\alpha$), are involved in the pathogenesis of these apical lesions. E. faecalis has been reported to stimulate macrophages to produce TNF-$\alpha$. The present study investigated the mechanisms involved in TNF-$\alpha$ production by a murine macrophage cell line, RAW 264.7 in response to exposure to E. faecalis. Both live and heat-killed E. faecalis induced high levels of gene expression and protein release of TNF-$\alpha$. Treatment of RAW 264.7 cells with cytochalasin D, an inhibitor of endocytosis, prevented the mRNA up-regulation of TNF-$\alpha$ by E. faecalis. In addition, antioxidant treatment reduced TNF-$\alpha$ production to baseline levels. Inhibition of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase also significantly attenuated E. faecalis-induced TNF-$\alpha$ expression by RAW 264.7 cells. Furthermore, activation of NF-${\kappa}B$ and AP-1 in RAW 264.7 cells was also stimulated by E. faecalis. These results suggest that the phagocytic uptake of bacteria is necessary for the induction of TNF-$\alpha$ in E. faecalis-stimulated macrophages, and that the underlying intracellular signaling pathways involve reactive oxygen species, ERK, p38 MAP kinase, NF-${\kappa}B$, and AP-1.

• KSBB Journal
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• v.25 no.1
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• pp.11-17
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• 2010

Here, we evaluated the effect of thrombin on the interleukin-6 production induced by tumor-necrosis-factor-$\alpha$ in endothelial cells. It is well known that tumor-necrosis-factor-$\alpha$ mediates inflammatory responses by activation of nuclear factor-kappa-B in endothelial cells. Here, we showed that lower concentration of thrombin decreased the production of interleukin-6 induced by tumor-necrosis-factor-$\alpha$ and this inhibitory effect of thrombin on interleukin-6 production was mediated by interacting with protease-activated-receptor-1. In addition, phosphoinositide-3-kinase was also involved the anti-inflammatory responses by lower concentration of thrombin in endothelial cells. These results suggested that lower concentration of thrombin mediated anti-inflammatory responses by interacting with protease-activated-receptor-1 on the cell membrane and phosphoinositide-3-kinase in the cell. These findings will provide the important evidence in the development of new medicine for the treatment of severe sepsis and inflammatory diseases and good clue for understanding unknown mechanisms by which thrombin showed the pro-inflammatory or anti-inflammatory activities in endothelial cells.

• BMB Reports
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• v.48 no.10
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• pp.559-564
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• 2015

We investigated the effects of mangiferin on the expression and activity of metalloproteinase (MMP)-9 and the invasion of tumor necrosis factor (TNF)-$\alpha$-stimulated human LNCaP prostate carcinoma cells. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that mangiferin significantly reversed TNF-$\alpha$-induced mRNA and protein expression of MMP-9 expression. Zymography data confirmed that stimulation of cells with TNF-$\alpha$ significantly increased MMP-9 activity. However, mangiferin substantially reduced the TNF-$\alpha$-induced activity of MMP-9. Additionally, a matrigel invasion assay showed that mangiferin significantly reduced TNF-$\alpha$-induced invasion of LNCaP cells. Compared to untreated controls, TNF-$\alpha$-stimulated LNCaP cells showed a significant increase in nuclear factor-${\kappa}B$ (NF-${\kappa}B$) luciferase activity. However, mangiferin treatment markedly decreased TNF-$\alpha$-induced NF-${\kappa}B$ luciferase activity. Furthermore, mangiferin suppressed nuclear translocation of the NF-${\kappa}B$ subunits p65 and p50. Collectively, our results indicate that mangiferin is a potential anti-invasive agent that acts by suppressing NF-${\kappa}B$-mediated MMP-9 expression.

• Journal of Periodontal and Implant Science
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• v.40 no.3
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• pp.119-124
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• 2010

Purpose: In addition to regulating body weight, leptin is also recognized for its role in the regulation of immune function and inflammation. The purpose of this study was to investigate the effect of leptin on Prevotella (P.) intermedia lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-$\alpha$ production in differentiated THP-1 cells, a human monocytic cell line. Methods: LPS from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. The amount of TNF-$\alpha$ and interleukin-8 secreted into the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). TNF-$\alpha$ and Ob-R mRNA expression levels were determined by semi-quantitative reverse transcription-polymerase chain reaction analysis. Results: Leptin enhanced P. intermedia LPS-induced TNF-$\alpha$ production in a dose-dependent manner. Leptin modulated P. intermedia LPS-induced TNF-$\alpha$ expression predominantly at the transcriptional level. Effect of leptin on P. intermedia LPS-induced TNF-$\alpha$ production was not mediated by the leptin receptor. Conclusions: The ability of leptin to enhance P. intermedia LPS-induced TNF-$\alpha$ production may be important in the establishment of chronic lesion accompanied by osseous tissue destruction observed in inflammatory periodontal disease.

• Journal of Periodontal and Implant Science
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• v.24 no.1
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• pp.155-164
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• 1994

치조골흡수는 만성치주질환의 전형적인 증상이다. 골흡수에 작용하는 여러 요인들 중에서도, 특히 최근에 들어서 몇몇 cytokine들에 대한 관심이 높아지고 있는데, interleukin-1(IL-1), tumor necrosis factor(TNF) 및 interleukin-6(IL-6) 등이 치주질환의 진행과정에서 중요한 치조골흡수요인으로 제안되고 있다. 본 연구의 목적은 신생쥐의 골조직 배양실험을 통해서 recombinant human $interleukin-1{\beta}$ ($rHuIL-1{\beta}$), recombinant human tumor necrosis $factor-{\alpha}$($rHuTNF-{\alpha}$) 및 recombinant human interleukin-6(rHuIL-6) 의 골흡수 유도효과를 알아보고, cyclooxygenase 억제제인 indomethacin과 recombinant murine $interferon-{\gamma}$($rMurIFN-{\gamma}$)가 이들 cytokine의 골흡수 유도능력에 미치는 영향을 알아봄으로써 이들 cytokine의 작용기구에 대해서 알아보고자 하는데 있다. 생후 1-2일된 쥐에게 $1{\mu}Ci^{45}CaCl_2$를 피하주사하고 4일 후에 쥐를 희생시켜 $^{45}Ca$ 로 표지된 두개골을 얻어 24시간 전배양 후, 각 cytokine ($rHuIL-1{\beta}$, $rHuTNF-{\alpha}$ 및 rHuIL-6)과 cytokine 및 첨가약제 (indomethacin 및 $rMurIFN-{\gamma}$)가 함유된 배지로 교환하여 48시간 배양한다. 골흡수 유도효과는 두개골에서 48시간의 배양 중 유리되는 $^{45}Ca$의 방사능 정도로 평가하였다. 본 연구를 통해 다음과 같은 결과를 얻었다. 1. $rHuIL-1{\beta}$ ($10^{-12}-10^{-9}M$) 및 $rHuTNF-{\alpha}$ ($10^{-10}-10^{-8}M$)는 농도변화에 따르는 골흡수 유도효과를 보였으나 , rHuIL-6 ($10^{-10}-10^{-8}M$)는 유의할 만한 효과를 보이지 않았다. 2. Indomethacin ($10^{-6}M$)은 $rHuIL-1{\beta}$ 및 $rHuTNF-{\alpha}$의 골흡수 유도작용에 유의할 만한 억제효과를 나타내지 않았다. 3. $rMurIFN-{\gamma}$ (1000 U/ml) 은 $rHuIL-1{\beta}$ 및 $rHuTNF-{\alpha}$의 골흡수 유도작용에 유의한 억제효과를 나타내었다. 본연구를 통해 치주질환 환자의 치주조직에서 검출되는 $IL-1{\beta}$ 및 $TNF-{\alpha}$가 치조골 흡수에 중요한 역할을 할 것으로 생각된다.

• 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.

• 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.