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

• Journal of Life Science
• /
• v.29 no.11
• /
• pp.1251-1257
• /
• 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 Applied Pharmacology
• /
• 2003.11a
• /
• pp.99-99
• /
• 2003

We studied the effect of Rubus croceacanthus Leveille (RCL) on mast cell-mediated anaphylactic reactions. RCL inhibited compound 48/80-induced systemic anaphylactic shock. When RCL was given at concentrations ranging from 0.01 to 1 mg/$m\ell$, the histamine release from rat peritoneal mast cells induced by compound 48/80 was reduced in a dose-dependent manner. RCL also inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl IgE. In addition, RCL inhibited phorbol 12-myristate 13-acetate and A23187-induced tumor necrosis factor-${\alpha}$ secretion from human mast cell line HMC-1 cells. These results indicate that RCL may possess a strong anti-anaphylactic activity.

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

• Korean Journal of Clinical Pharmacy
• /
• v.28 no.4
• /
• pp.333-341
• /
• 2018

Objective: Tumor necrosis factor-alpha (TNF-alpha) inhibitors are used as a treatment in various immune-mediated inflammatory diseases (IMIDs). Tuberculosis (TB) risk is reported in several meta-analyses in patients treated with TNF-alpha inhibitors. The purpose of this study is to collect, review, and evaluate the TB risk in TNF-alpha inhibitors according to IMIDs indications and between soluble-receptor TNF-alpha inhibitor and monoclonal-antibody TNF-alpha inhibitors. Methods: A systematic literature search on systematic reviews and meta-analyses was performed in PubMed, MEDLINE, Cochrane library, and EMBASE. We identified meta-analyses that evaluated TB infection risk of TNF-alpha inhibitors in IMIDs patients. Results: Thirteen meta-analyses including 41 study results were included in this umbrella review. IMIDs patients treated with TNF-alpha inhibitors had an increased risk of TB than control group (placebo with or without standard therapy patients) (relative risk ratio (RR) 2.057, 95% confidence interval (CI) 1.697 to 2.495). Among them, RA patients with TNF-alpha inhibitors had a higher risk of TB than control group (RR 1.847, 95% CI 1.385 to 2.464), and non-RA patients with TNF-alpha inhibitors had an increased risk of TB (RR 2.236, 95% CI 1.284 to 3.894). In subgroup analysis on TB risk between soluble-receptor TNF-alpha inhibitor and monoclonal-antibody TNF-alpha inhibitors in RA patients, the analysis indicated that monoclonal-antibody TNF-alpha inhibitors had higher risk of TB than soluble-receptor TNF-alpha inhibitor (RR 2.880, 95% CI 1.730 to 4.792). Conclusion: This umbrella review confirms that the risk of TB is significantly increased in TNF-alpha inhibitor treated patients compared to control group.

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

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

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

• BMB Reports
• /
• v.47 no.5
• /
• pp.280-285
• /
• 2014

Cancer cells undergo uncontrolled proliferation, and aberrant mitochondrial alterations. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial heat shock protein. TRAP1 mRNA is highly expressed in some cancer cell lines and tumor tissues. However, the effects of its overexpression on mitochondria are unclear. In this study, we assessed mitochondrial changes accompanying TRAP1 overexpression, in a mouse cell line, NIH/3T3. We found that overexpression of TRAP1 leads to a series of mitochondrial aberrations, including increase in basal ROS levels, and decrease in mitochondrial biogenesis, together with a decrease in peroxisome proliferator-activated receptor gamma coactivator-$1{\alpha}$ (PGC-$1{\alpha}$) mRNA levels. We also observed increased extracellular signal-regulated kinase (ERK) phosphorylation, and enhanced proliferation of TRAP1 overexpressing cells. This study suggests that overexpression of TRAP1 might be a critical link between mitochondrial disturbances and carcinogenesis.

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