• Clinical and Experimental Pediatrics
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• v.56 no.3
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• pp.116-124
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• 2013

Purpose: Tumor necrosis factor (TNF)-${\alpha}$ is thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-${\alpha}$ antagonist) treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model. Methods: Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C), single subcutaneous injection of normal saline (0.1 mL/kg); monocrotaline (M), single subcutaneous injection of monocrotaline (60 mg/kg); and monocrotaline + infliximab (M+I), single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg). The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-${\alpha}$, endothelin-1 (ET-1), endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP) 2, and tissue inhibitor of matrix metalloproteinase (TIMP). Results: The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P<0.05). The number of intraacinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P<0.05). Expression levels of TNF-${\alpha}$, ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28). Conclusion: Infliximab administration induced early changes in pathological findings and expression levels of TNF-${\alpha}$, and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.

• Nutrition Research and Practice
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• v.1 no.4
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• pp.285-290
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• 2007

The leukocyte recruitment and transmigration across the endothelial barrier into the vessel wall are crucial steps in atherosclerosis. Leukocyte trafficking on the endothelium is elicited by induction of endothelial adhesion molecules, and its transmigration is mediated by degradation of basement membrane proteins through enzymatic activity of matrix metalloproteinases (MMP). The current study investigated whether resveratrol, a polyphenol present in grapes and red wine, was capable of inhibiting leukocyte adhesion to tumor necrosis factor (TNF)-${\alpha}$-activated endothelium. It was found that resveratrol inhibited the TNF-${\alpha}$-activated endothelial expression of vascular cell adhesion molecule-1 in a dose-dependent manner. In addition, resveratrol hampered THP-1 monocyte adhesion to activated endothelial cells. This study further examined whether resveratrol interfered with transendothelial migration of leukocytes. The MMP-2 gelatinolytic activity of endothelial cells was enhanced by TNF-${\alpha}$, which was attenuated by an addition of ${\geq}25{\mu}M$ resveratrol. In addition, 25 ${\mu}M$ resveratrol mitigated the MMP-9 activity of THP-1 cells, followed by a marked inhibition of transendothelial migration. These results demonstrated that resveratrol suppressed monocyte adhesion and migration induced by TNF-${\alpha}$ through modulating expression of adhesion molecules and gelatinolytic activity of MMP. These findings suggest that dietary resveratrol may be therapeutic agent for inhibiting leukocyte recruitment into the subendothelium during inflammatory atherosclerosis.

• Toxicological Research
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• v.20 no.3
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• pp.233-239
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• 2004

The present study was designed to determine the impact of mercury on endotoxin-induced inflammatory cytokine expression and corresponding signal transduction in mouse kidney. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercury in drink-ing water for 14 days and at the end of the treatment period, lipopolysaccharide (LPS, 0.5 mg/kg) was injected intraperitoneally 2 h prior to euthanasia. The doses of mercury and LPS did not cause hepatotoxicity or renal toxicity as indicated by unaltered plasma alanine aminotransferase and aspartate aminotransferase levels, and terminal UTP nucleotide end-labeling assay from kidney, respectively. Mercury decreased kidney glutathione (GSH) and with LPS, it additively decreased GSH. Mercury activated p38 mitogen-activated protein kinase (MAPK) and additively increased LPS-induced p38 MAPK phosphorylation. In contrast, mercury inhibited LPS-induced activation of extra-cellular signal-regulated kinase (ERK) but had no effect alone. Mercury increased the gene expression of tumor necrosis factor $\alpha$ (TN F$\alpha$) and potentiated LPS-induced TNF$\alpha$ expression. Mercury did not affect LPS-induced interleukin-1$\beta$ (IL-1$\beta$) expression but decreased LPS-induced IL-6 expression. These results suggest that low levels of mercury might augment LPS-induced TNF$\alpha$ expression by altering GSH and p38 MAPK. Mercury modulates LPS-induced p38 and ERK activation, and downstream TNF$\alpha$ and IL-6 expression in kidney, respectively.

• Journal of the Korean Society of Radiology
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• v.10 no.3
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• pp.195-200
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• 2016

Acute promyelocytic leukemia(APL) is not just the poor grades of treating a type of blood cancer hayeoteul combination with chemotherapy despite concurrent radiation therapy are known to exhibit a greater effect and also works on normal cells to result in side effects. In this study, when after treatment with gamma rays, such as $TNF-{\alpha}$ in order to reduce these side effects was confirmed how affected the cell death of normal cells and cancer cells. HL-60 cells were used as the APL cell line HL-60 cells were differentiated with DMSO for treatment are shown the properties of normal granulocytes was used as a control group. As a result, HL-60 cells treated with $TNF-{\alpha}$ and gamma rays with only showed a cytotoxic effect by inducing the apoptosis cells were put to death. Consequently, $TNF-{\alpha}$ is thought to active substances that can increase the efficiency of cancer treatment to increase the removal of cancer cells when used with low-density gamma-ray treatment in order to eliminate the side effects of chemotherapy.

• Journal of Korean Medicine for Obesity Research
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• v.18 no.2
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• pp.74-82
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• 2018

Objectives: The objective of this study is to investigate the effects of Silbi-um (SBU) extract on the alcoholic fatty liver induced by EtOH administration for 8 weeks. Methods: Male Sprague Dawley rats were used. All animals were randomly divided into 3 groups; Normal, EtOH and EtOH+SBU. The rats of EtOH group were daily treated with ethanol of 25% (v/v) for 8 weeks (n=10). EtOH+SBU group was orally treated with SBU water extract after ethanol administration (n=10). The rats of Normal group were treated with saline (n=10). After 8 weeks, the mean body weight, liver weight, and liver-body weight ratio were calculated. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of all groups were measured. The morphological alterations were observed using hematoxylin and eosin (H&E) and Oil Red O staining. Moreover, the alteration of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) levels were analyzed immunohistochemistrically. Results: The histological data showed that liver sections from EtOH group displayed severe steatosis. SBU extract significantly inhibited the progression of the alcoholic liver injury. The increased serum level of ALT and AST induced by ethanol administration were decreased by SBU extract. Furthermore, SBU extract significantly decreased the liver concentrations of $TNF-{\alpha}$. Conclusions: SBU water extract attenuated the alcohol induced fatty liver by improving hepatic lipid metabolism via suppression of $TNF-{\alpha}$ protein. SBU could be effective in protecting the liver from alcoholic fatty liver.

• Nutrition Research and Practice
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• v.10 no.3
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• pp.251-258
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• 2016

BACKGROUND/OBJECTIVES: Several pharmacological properties of red rice extract have been reported including anti-oxidant, anti-tumor, and reduced cancer cell invasion. This study was conducted to evaluate the anti-inflammatory effects of red rice extract on the production of inflammatory mediators in lipopolysaccharide (LPS)-induced Raw 264.7 macrophages. MATERIALS/METHODS: Pro-inflammatory cytokines including tumor necrosis factor-${\alpha}$ and interleukin-6 were determined by ELISA and cyclooxygenase-2 and inducible nitric oxide synthase expression was evaluated using western blot analysis. In addition, the signaling pathway controlling the inflammatory cascade such as nuclear factor kappa B ($NF-{\kappa}B$), activator proteins-1 (AP-1), and mitogen-activated protein kinase (MAPK) was determined. RESULTS: Our results showed that red rice polar extract fraction (RR-P), but not non-polar extract fraction, inhibited interleukin-6, tumor necrosis factor-${\alpha}$, and nitric oxide production in LPS-induced Raw 264.7 cells. RR-P also reduced the expression of inflammatory enzymes, inducible nitric oxide synthase, and cyclooxygenase-2. In addition, activation of AP-1 and $NF-{\kappa}B$ transcription factor in the nucleus was abrogated by RR-P. RR-P inhibited the phosphorylation of extracellular signaling-regulated kinase 1/2, c-Jun NH2-terminal kinase, and p38 MAPK signaling responsible for the expression of inflammatory mediators in LPS-stimulated Raw 264.7 cells. Based on chemical analysis, high amounts of proanthocyanidin and catechins were detected in the RR-P fraction. However, only proanthocyanidin reduced $NF-{\kappa}B$ and AP-1 activation in LPS-activated Raw 264.7 cells. CONCLUSION: These observations suggest that the anti-inflammatory properties of RR-P may stem from the inhibition of pro-inflammatory mediators via suppression of the AP-1, $NF-{\kappa}B$, and MAPKs pathways.

• Journal of Veterinary Clinics
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• v.29 no.5
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• pp.361-367
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• 2012

Diabetes-related complications in human and veterinary medicine have been shown to be associated with hyperglycemia-induced inflammation. It has been recently suggested that the onset of insulin resistance may be caused by over-production of inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$ from immune cells. Conjugated linoleic acid (CLA) regulates inflammatory response through modulation of TNF-${\alpha}$ expression. The objective of this study was to examine the effect of CLA on nuclear factor kappaB (NF-${\kappa}B$) p65 binding activity, inhibitory kappaB ($I{\kappa}B$)-${\alpha}$ expression, and TNF-${\alpha}$ production from high glucose-treated RAW 264.7 cells. CLA was added to RAW cells that had been previously cultured with low or high concentration of glucose. The levels of TNF-${\alpha}$ protein in the culture supernatant of RAW cells exposed to high concentrations of glucose were higher than those of cells exposed to low concentrations of glucose. The treatment with the high concentration of glucose in RAW cells increased levels of NF-${\kappa}B$ p65 binding activity and the decreased $I{\kappa}B-{\alpha}$ expression when compared with those of low glucose. The treatments in combination with CLA and glucose (low and high) glucose in RAW cells increased TNF-${\alpha}$ production when compared with that glucose alone. These treatments with CLA increased TNF-${\alpha}$ production in high glucose-treated RAW cells than those with low glucose. These treatments of CLA also showed higher NF-${\kappa}B$ p65 binding activity and lower $I{\kappa}B-{\alpha}$ expression in high glucose than those in low glucose condition. This suggests that CLA can increase NF-${\kappa}B$ p65 binding activity and TNF-${\alpha}$ production from high glucose-treated RAW 264.7 cells and is likely to promote hyperglycemia-induced inflammation.

• Journal of Genetic Medicine
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• v.6 no.2
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• pp.155-160
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• 2009

Purpose: Preeclampsia is a multisystem human pregnancy-specific disorder. The pathophysiology of preeclampsia is linked with over-stimulation of inflammatory cytokines by placental ischemia via reduced uterine perfusion pressure during pregnancy. Although an increase in tumor necrosis factor (TNF)-alpha has been reported in preeclamptic women, there is little evidence of a relationship between TNF-alpha gene variations and preeclampsia. In this study, we identified a single-nucleotide polymorphism (SNP), C-850T, in the TNF-alpha gene promoter region in Korean preeclamptic women and investigated the association between this SNP and the development of preeclampsia. Materials and Methods: This polymorphism was analyzed in peripheral blood samples from 198 preeclamptic pregnancies and 194 normotensive pregnancies using a SNapShot kit and an ABI Prism 3100 Genetic analyzer. Results: Genotypes and allele frequencies for C-850T did not differ between preeclamptic and normotensive pregnancies. The distributions of genotypes (CC, CT and TT) were 74.3%, 22.2% and 3.5%, respectively, in preeclamptic pregnancies, and 71.6%, 25.8% and 2.6%, respectively, in normotensive pregnancies. The frequencies of the C and T alleles were 0.85 and 0.15 in preeclamptic pregnancies and 0.84 and 0.16 in normotensive pregnancies, respectively. There was no increased risk of preeclampsia in subjects with the CT (OR, 0.83; P=0.44) or TT genotypes (OR, 1.32; P=0.64). Conclusion: We found no differences in the genotypes or allele frequencies of the TNF-alpha gene polymorphism between preeclamptic and normotensive pregnancies. This study suggests that the TNF-alpha gene polymorphism may be not associated with the development of preeclampsia in pregnant Korean women.

• Proceedings of the Korean Aquaculture Society Conference
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• 2006.05a
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• pp.504-505
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• 2006

• Proceedings of the Korean Society of Food Hygiene and Safety Conference
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• 2001.10a
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• pp.223-226
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• 2001