• Radiation Oncology Journal
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• v.16 no.3
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• pp.225-231
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• 1998

Purpose : To determine whether TNF-$\alpha$ increases the antitumor effect of radiotherapy in murine syngeneic tumor system. Materials and Methods : Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I(hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter mice were treated with TNF-$\alpha$, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-$\alpha$ mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 ug per mouse for 7 days. In combination of radiation and TNF-$\alpha$, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment. Results : Among 4 tested tumors, TNF-$\alpha$ alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-$\alpha$ showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-$\alpha$ alone and radiation, i.e., 6.5 days and 26.9 days, respectively(p<0.05). Enhancement factor was 1.29 in OCa-I, which showed supraadditive effect. TNF-$\alpha$ did not show significant delay of AGDs in the remaining 3 tumors compared to AGDs of TNF-$\alpha$ alone and radiation. Conclusions: TNF-$\alpha$ alone showed antitumor effects in MCa-K and OCa-I. In combination with radiation, TNF-$\alpha$ acted in supraadditive way in OCa-I only. The results of this study imply that the combination of TNF-$\alpha$ and radiation has different therapeutic potential depending on tumor model and further study is advocated.

• Advances in Traditional Medicine
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• v.10 no.1
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• pp.7-12
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• 2010

Typha orientalis' stem (TOS) is traditionally used as an herbal medicine for difficulty in urination, galactophoritis purulenta, whooping cough, and allergic dermatitis. However, its effect in experimental models remains unknown. Here, we report the effect of TOS on the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-induced inflammatory cytokine production and extracellular signal-regulated kinase (ERK) activation in the human mast cell line, HMC-1. TOS inhibited PMA plus A23187-induced cytokines such as tumor necrosis factor-alpha (TNF-$\alpha$) and interleukin (IL)-6. Maximal inhibition rate of TNF-$\alpha$ and IL-6 production by TOS (1 mg/ml) was about 44.02%, and 45.20%, respectively (P < 0.05). In addition, TOS inhibited the expression of TNF-$\alpha$ and IL-6 mRNA under the same condition. Moreover, TOS partially blocked PMA plus A23187-induced ERK phosphorylation. These results suggested TOS could inhibit the cytokine production through blocking of ERK activity.

• Journal of Periodontal and Implant Science
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• v.42 no.1
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• pp.3-12
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• 2012

Purpose: Anti-rheumatic agents target common molecular pathways of inflammation in rheumatoid arthritis (RA) and periodontitis. The purpose of this study was to determine the relative effect of anti-rheumatic agents on the levels of inflammatory biomarkers and periodontal inflammation in RA patients with periodontitis. Methods: A systematic review and meta-analysis were conducted of studies comparing periodontal parameters of inflammation, such as bleeding on probing, and biomarkers of inflammation in RA patients with periodontitis and healthy adults with and without periodontitis. The search included the electronic databases MEDLINE, Cochrane Database of Systematic Reviews, and Google Scholar, inclusive through October 2011, with no language restrictions. Hand searches were conducted of the bibliographies of related journals and systematic reviews. Observational and interventional studies assessing the effects of antirheumatic therapy qualified for inclusion. Two reviewers performed independent data extraction and risk-of-bias assessment. Of the 187 identified publications, 13 studies fulfilled the inclusion criteria. Results: When compared to healthy adults without periodontitis, RA subjects were found to have significantly higher levels of bleeding on probing and limited evidence of higher levels of interleukin-$1{\beta}$ and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in gingival crevicular fluid and saliva. No consistent differences were found in periodontal parameters and inflammatory biomarkers between RA subjects and adults with periodontitis. Studies evaluating the effect of anti-TNF-${\alpha}$ therapy in RA subjects with periodontitis have yielded inconsistent results. Conclusions: There are limited data, however, to suggest that anti-TNF-${\alpha}$ agents can reduce local production of inflammatory cytokines and periodontal inflammation in RA patients with periodontitis.

• Journal of Life Science
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• v.18 no.11
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• pp.1471-1478
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• 2008

In this study, nitric oxide (NO) production in a macrophage-lymphocyte co-culture system was used to assess the cytokine producing capability of cells during endotoxin tolerance in mice. Incubation of peritoneal macrophages with interferon-$\tau$ (IFN-$\tau$) in the presence of lipopolysaccharide (LPS) augmented NO synthesis. Exogenous tumor necrosis factor-$\alpha$(TNF-$\alpha$) could also replace LPS for the stimulation of NO production. Macrophages co-cultured with splenic lymphocytes showed augmented NO synthesis by LPS alone. However, pretreatment of mice with 2.5 mg/kg LPS completely prevented the lethality and the increase of blood TNF-$\alpha$ and IFN-$\tau$ after the second challenge with a lethal dose of LPS. In addition, when macrophages prepared from LPS-tolerant mice were co-cultured with normal splenocytes, LPS also could not induce the production of NO, even in the presence of exogenous TNF-$\alpha$. Moreover, when normal macrophages were co-cultured with splenocytes obtained from LPS-tolerant mice, stimulation with LPS could not evoke the NO production enhancement. However, this down-regulation was able to reverse by exogenous IFN-$\tau$ or concanavalin A (ConA), a stimulator of IFN-$\tau$ production. Our results indicate that not only macrophages but also lymphocytes contribute to LPS tolerance. As INF-$\tau$ can enhance the expression of TNF-$\alpha$, the decrease of INF-$\tau$synthesis from lymphocytes may orchestrate with the decrease of TNF-$\alpha$ synthesis from LPS-tolerant macrophages for the production of tolerant state and the prevention of excessive inflammation. Therefore, LPS tolerance may be exploited for prophylaxis of severe sepsis in patients at risk.

• BMB Reports
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• v.37 no.2
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• pp.185-191
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• 2004

Tissue transglutaminase (tTGase) regulates various biological processes, including extracellular matrix organization, cellular differentiation, and apoptosis. Here we report the protective role of tTGase in the cell death that is induced by the tumor necrosis factor $\alpha$ (TNF-$\alpha$) and ceramide, a product of the TNF-$\alpha$ signaling pathway, in human neuroblastoma SH-SY5Y cells. Treatment with retinoic acid (RA) induced the differentiation of the neuroblastoma cells with the formation of extended neurites. Immunostaining and Western blot analysis showed the tTGase expression by RA treatment. TNF-$\alpha$ or $C_2$ ceramide, a cell permeable ceramide analog, induced cell death in normal cells, but cell death was largely inhibited by the RA treatment. The inhibition of tTGase by the tTGase inhibitors, monodansylcadaverine and cystamine, eliminated the protective role of RA-treatment in the cell death that is caused by TNF-$\alpha$ or $C_2$-ceramide. In addition, the co-treatment of TNF-$\alpha$ and cycloheximide ecreased the protein level of tTGase and cell viability in the RA-treated cells, supporting the role of tTGase in the protection of cell death. DNA fragmentation was also induced by the co-treatment of TNF-$\alpha$ and cycloheximide. These results suggest that tTGase expressed by RA treatment plays an important role in the protection of cell death caused by TNF-$\alpha$ and ceramide.

• Clinical and Experimental Pediatrics
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• v.48 no.8
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• pp.871-876
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• 2005

Purpose : Recently, it was reported that tumor necrosis factor(TNF) and $lymphotoxin-{\alpha}$($LT-{\alpha}$) gene regions might be a susceptible loci to type 1 diabetes in Japanese. The purpose of this study was to investigate the association of TNF and $LT-{\alpha}$ gene polymorphisms with disease susceptibility in Korean children with type 1 diabetes. Methods : Forty-nine Korean children with type 1 diabetes(29 girls and 20 boys) and 94 healthy Koreans were investigated in this study. Genotyping for -857T/C polymorphism in the TNF promoter region and $LT-{\alpha}$ gene polymorphism were performed by PCR-RFLP(restriction fragment length polymorphism). TNF promoter -1031C/T polymorphism was detected by allele-specific PCR. Results : The distribution of the -857T/C and -1031C/T genotype in the TNF promoter region was not different between diabetic children and the controls. The frequency of TT genotype in the distribution of TNF -1031C/T polymorphism in diabetic children with diabetic ketoacidosis(DKA) at diagnosis was significantly lower than those without DKA(P<0.05). No significant difference in the distribution of $LT-{\alpha}$ gene polymorphism was observed between diabetic children and the controls. There was no association between clinical characteristics of type 1 diabetes and $LT-{\alpha}$ gene polymorphisms. Conclusion : These results suggest that TNF promoter -857T/C and $LT-{\alpha}$ gene polymorphisms are not associated with susceptibility to type 1 diabetes in Korean children. TNF promoter -1031C/T polymorphism might be related to clinical manifestations(DKA) of type 1 diabetes.

• Biomedical Science Letters
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• v.19 no.2
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• pp.118-123
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• 2013

Tumor necrosis factor-alpha (TNF-${\alpha}$) is a proinflammatory cytokine that mediates the inflammatory response and immune functions, and modulates the proliferation, differentiation and cell death of cancer cells. The differential functions of TNF-${\alpha}$ in various human cells due to the formation of different stimulating pathway upon the binding of TNF-${\alpha}$ to its receptors. In the present study, we examined the different effects of TNF-${\alpha}$ on the survival and apoptosis between normal granulocytes and human myeloid leukemia HL-60 cells. Although TNF-${\alpha}$ did not affect on the constitutive apoptosis of granulocytes, TNF-${\alpha}$ strongly induced the apoptosis of HL-60 cells in a dose- and a time-dependent manner. TNF-${\alpha}$-induced apoptosis was occurred via the activation of caspase 8, caspase 9 and caspase 3/7 and the induction of ROS production in HL-60 cells. Also, BAY-11-7085, a NF-${\kappa}B$ inhibitor, blocked the TNF-${\alpha}$-induced apoptosis in HL-60 cells. NF-${\kappa}B$ may be involved in TNF-${\alpha}$-induced apoptotic signaling pathway in HL-60 cells. These results suggest that TNF-${\alpha}$ activates apoptotic pathways and its process depends on cell type and many cellular factors. A better understanding of the differential effect of TNF-${\alpha}$ on cell apoptosis and survival may provide important information that can be used to elucidate the specific inhibitory effect of TNF-${\alpha}$ on the cancer dis.

• Natural Product Sciences
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• v.13 no.4
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• pp.337-341
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• 2007

In this report, we investigated the effect of aqueous extract of vinegar treated small black soybean (Glycine max Merr.) (Leguminosae) (VSBS) on mast cell-mediated allergic reaction and pro-inflammatory cytokine secretion. VSBS inhibited compound 48/80-induced systemic reactions. VSBS attenuated immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis. In addition, VSBS decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated secretion of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6 and interleukin (IL)-8 in human mast cells. Our findings provide evidence that VSBS inhibits mast cell-derived allergic reactions.

• Journal of Life Science
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• v.23 no.9
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• pp.1140-1146
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• 2013

The effect of dried mackerel extract on the production of nitric oxide (NO) and cytokines, including interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was investigated. All extracts and fractions from dried mackerel significantly reduced NO production induced by lipopolysaccharide (LPS). Among the extracts, acetone+methylene chloride (A+M), n-hexane, and 85% aqueous methanol (MeOH) showed the strongest inhibitory effects. The 85% aqueous MeOH fraction at a concentration of $10{\mu}g$ significantly decreased LPS-induced IL-6 and TNF-${\alpha}$ production after 6 hr of incubation. In the case of LPS-induced IFN-${\gamma}$ production, the 85% aqueous MeOH fraction decreased the production of IFN-${\gamma}$ afer 6, 24, and 72 hr of incubation in a dose-dependent manner. The results show that an 85% aqueous MeOH fraction inhibits the production of NO and proinflammatory cytokines (IL-6, TNF-${\alpha}$, IFN-${\gamma}$), suggesting that this fraction acts as a potent immunomodulator.

• Korean Journal of Clinical Pharmacy
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• v.25 no.4
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• pp.246-253
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• 2015

Background & Object: Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes ankylosis and deformation of axial joints. Since current medicine cannot cure the disease yet, alleviating pain and preventing deformation with medications are the main therapy for patients with AS. The key medications for these purposes include nonsteroidal anti-inflammatory drugs (NSAIDs), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) inhibitors. This study aims to analyze prescribing patterns of AS patients in South Korea. Method: National Patients Sample data compiled by the Health Insurance Review and Assessment Service from 2013 was analyzed. Patients with AS were identified with Korean Standard Classification of Diseases code-6, which was M45. The rates of prescription, discontinuation, and switching ingredients were calculated for each medication during 2013. Results: Total number of patients was 655, and most of them were male (n = 514, 78.5%). Of all age groups, the proportion of 30-40 year old patients was the greatest (35.1%). The most utilized drug class was NSAIDs (82.4%). Less than half of patients were prescribed $TNF-{\alpha}$ inhibitors (n = 212, 32.4%). Meloxicam, aceclofenac, and celecoxib were the most frequently prescribed NSAIDs. In case of $TNF-{\alpha}$ inhibitors, adalimumab, etanercept and infliximab were the top three most prescribed drugs. Although not recommended by the current practice guideline, significant proportions of patients were identified using disease modifying anti-rheumatic drugs (DMARDs). Conclusion: Considering the current practice guideline and previous studies about the efficacy, the use of DMARDs should be reduced and medical insurance term in South Korea should be re-examined.