• Korean Journal of Pharmacognosy
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• v.45 no.3
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• pp.256-261
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• 2014

Bee venom (BV) therapy has been used as a traditional medicine to treat a variety of conditions, such as arthritis, back pain, cancerous tumors, and skin diseases. However, regulatory effects of BV on tumor necrosis factor (TNF)-${\alpha}$-induced HaCaT cell migration or anti-inflammatory have not been explored. In the present study, we investigated the effects of BV on HaCaT cell migration and anti-inflammation. HaCaT cell migration was evaluated by wound-healing assay. The pro-inflammatory cytokines such as TNF-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-8 were examined by ELISA or Western blotting. BV treatment led to an increase in migration of HaCaT cells for 24 and 48 h. Especially, 10 ng/ml of BV were significantly increased HaCaT cell migration. Also, BV suppressed the secretion of TNF-${\alpha}$, IL-$1{\beta}$, and IL-8 in culture medium with HaCaT cells. In addition, Western blot results demonstrate that BV suppressed the expression of TNF-${\alpha}$ and IL-$1{\beta}$, in HaCaT cells. Especially, 1 or 10 ng/ml of BV markedly decreased the expression of pro-inflammatory cytokines. These results demonstrate the potential of BV for the prevention of skin inflammation induced by TNF-${\alpha}$.

• Journal of Chest Surgery
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• v.32 no.11
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• pp.971-977
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• 1999

Background: Immunologic and inflammatory responses of cardiopulmonary bypass(CPB) influence postoperative mortality and morbidity with multiple organ injury. It has been reported that ischemia/reperfusion induced-myocardial injury during CPB is causative of release of inflammatory cytokines such as interleukin-6(IL-6) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$). The purpose of this study was to detect the time course of the activated cytokine and troponin-T(TnT), and to examine the correlation between such parameters during CPB. Material and Method: The serial samples were collected from arterial blood via radial arterial catheter in 23 patients who are underwent open heart surgery (OHS) with CPB, the IL-6, TNF-$\alpha$ and TnT were checked. Result: \circled1 IL-6, TNF$\alpha$- and TnT concentration increased significantly during CPB with a peaking level of CPB-off (p 0.05). \circled2 IL-6 had highly positive correlation with aortic cross clamping time and total bypass time(r=0.80, 0.78; p 0.05, respectively). \circled3 There was no correlation among IL-6, TNF-$\alpha$ and TnT. Conclusion: In conclusion, these data showed that elevated production of serum IL-6 during CPB was attributable to ischemia/reperfusion induced-myocardial damage. IL-6 will become a new and sensitive biological marker in assessment of myocardial damage during OHS with CPB. However, further studies will be needed to apply IL-6 in more patient population.

• Journal of Korean Neurosurgical Society
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• v.57 no.2
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• pp.73-76
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• 2015

Objective : Tumor necrosis factor alpha (TNF-${\alpha}$) have proven effects in pathogenesis of neuroinflammation after spinal cord injury (SCI). Current study is designed to evaluate the effects of an anti-TNF-${\alpha}$ agent, adalimumab, on spinal cord clip compression injury in rats. Methods : Thirty two male adult Wistar rats were divided into four groups (sham, trauma, infliximab, and adalimumab groups) and SCI was introduced using an aneurysm clip. Animals in treatment groups received 5 mg/kg subcutaneous adalimumab and infliximab right after the trauma. Malondialdehyde (MDA) levels were studied in traumatized spinal cord tissues 72 hours after the injury as a marker of lipid peroxidation. Results : Animals that received anti-TNF-${\alpha}$ agents are found to have significantly decreased MDA levels. MDA levels were significantly different between the trauma and infliximab groups (p<0.01) and trauma and adalimumab groups (p=0.022). There was no significant difference in neurological evaluation of the rats using Tarlov scale. Conclusion : These results suggest that, like infliximab, adalimumab has favorable effects on lipid peroxidation induced by spinal cord trauma in rats.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.14 no.11
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• pp.5778-5784
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• 2013

In order to develop anti-wrinkle agent, we measured the anti-oxidative activity of gallic acid (GA) from Paeonia suffruticosa Andrews and investigated its cytotoxicity in HaCaT cells and then investigated its effect on tumor necrosis factor alpha (TNF-${\alpha}$)-induced matrix metalloproteinase-1 (MMP-1) mRNA, protein expressions and secretion in same cells. GA showed anti-oxidative activity with $IC_{50}$ of 30 ${\mu}g/mL$ and its activity was higher than that of butylated hydroxyanisol (BHA). GA showed weak cytotoxicity with high concentration (200 ${\mu}g/mL$) in HaCaT cells. MMP-1 mRNA, protein expression and secretion induced by tumor necrosis factor alpha (TNF-${\alpha}$) in HaCaT cells were significantly decreased by treatment of GA with dose-dependent manner(p<0.05). Therefore, our findings suggest that GA can be useful as an active ingredient for cosmeceuticals of anti-wrinkle effects.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.5
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• pp.269-274
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• 2002

A large number of factors such as osteotropic hormones, cytokines, or growth factors are related to the bone remodeling which is characterized by the coupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Recent investigations have indicated that cytokines such as $interleukin-1{\beta}\;(IL-1{\beta})$ and tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ play a potential role in the bone resorption associated with a variety of pathological conditions such as inflammatory osteolytic disease. Collagen is the most abundant protein of the extracellular matrix of bone, and the participation of collagenase in bone resorption has been widely investigated. In this study, effects of $IL-1{\beta}$ and $TNF-{\alpha}$ on the release of collagenase from osteoblastic cells were measured. The gelatinase activity was also measured by gel substrate analysis (zymography) after electrophoresis of conditioned media of osteoblastic cell culture. $IL-1{\beta}$ increased the collagenase activity in ROS17/2.8 and HOS cell culture. $TNF-{\alpha}$ also increased the collagenase activity of osteoblastic cells. When two kinds of cytokines were treated simultaneously in the culture of osteoblastic cells, synergistic increase of collagenase activity was seen in ROS17/2.8 cells. $IL-1{\beta}$ and $TNF-{\alpha}$ significantly increased the collagenase activity after 6 hour treatment in the osteoblastic cell culture, and there was no additional increase according to the culture period. Osteoblastic cells released the gelatinase and molecular weight of this enzyme was measured about 70 KDa as assessed by zymogram. $IL-1{\beta}$ and $TNF-{\alpha}$ showed increase of the gelatinase activity produced by ROS17/2.8 and HOS cells. Taken together, this study suggested that $IL-1{\beta}$ and $TNF-{\alpha}$ can modulate bone metabolism, at least in part, by increased release of collagenase and gelatinase from osteoblasts.

• Journal of Microbiology
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• v.39 no.3
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• pp.186-194
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• 2001

Scrub typhus, caused by Orientia tsutsugamushi infection, is clinically and histopathologically characterized by local as well as systemic inflammatory reactions, indicating that orientiae induce mechanisms that amplify the inflammatory response. To reveal underlying mechanisms of chemoattraction and activation of responding leukocytes, expression of chemokine and tumor necrosis factor alpha (TNF-$\alpha$) genes in murine peritoneal macrophages after infection with the obligate intracellular bacterium Ο.tsutsugamushi was investigated. The genes that were unregulated included macrophage inflammatory proteins l$\alpha$/$\beta$(MIP-l$\alpha$/$\beta$), MIP-2, monocyte chemoattractant protein 1(MCP-1), RANTES (regulated upon activation, normal T-cell expressed and secreted), gamma-interferon-inducible protein 10(IP-10) and TNF-$\alpha$. Peak expression of these chemokines and TNF-$\alpha$ was observed between 1 and 3 h after infection. These responses returned to or approached baseline preinfection levels 6 h after challenge. Semiquantitative reverse transcription (RT)-PCR analysis revealed dramatic Increases during infection in the steady-state levels of mRNA ceding for the inhibitory subunit of NF-kB (IkB$\alpha$), whose transcription is enhanced by binding of NF-kB within the IkB$\alpha$promoter region. Thus, Ο. tsutsugamushi appears to be a stung inducer of chemokines and TNF-$\alpha$ which may significantly contribute to inflammation and tissue damage observed in scrub typhus by attracting and activating phagocytic leukocytes.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1271-1284
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• 1997

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. However, since the efficiency of current techniques of gene transfer is not satisfactory, the majority of current protocols is aiming the in vitro gene transfer to cancer cells and re-introducing genetically modified cancer cells to host. In the previous study, it was shown that TNF-sensitive cancer cells transfected with TNF-$\alpha$ cDNA would become highly resistant to TNF, and the probability was shown that the acquired resistance to TNF might be associated with synthesis of some protective protein. Understanding the mechanisms of TNF-resistance in TNF-$\alpha$ cDNA transfected cancer cells would be an important step for improving the efficacy of cancer gene therapy as well as for better understandings of tumor biology. This study was designed to evaluate whether the levels of TNF receptor mRNA expression and soluble TNF receptor release from cancer cells are changed after TNF-$\alpha$ cDNA transfection. Method : We transfected TNF-$\alpha$ c-DNA to WEHI164(murine fibrosarcoma cell line), NCI-H2058(human mesothelioma cell line), A549(human non-small cell lung cancer cell line), ME180(human cervix cancer cell line) cells using retroviral vector(pLT12SN(TNF)) and confirm the expression of TNF with PCR, EUSA, MTT assay. Then we determined the TNF resistance of TNF-$\alpha$ cDNA transfected cells(WEHI164-TNF, NCIH2058-TNF, A549-TNF, ME180-TNF) and evaluated the TNF receptor mRNA expression with Northern blot analysis and soluble TNF receptor release with EUSA. Results : The TNF receptor mRNA expressions of parental cells and genetically modified cells were not significantly different. The soluble TNF receptor levels of media from genetically modified cells were lower than those from parental cells. Conclusion : The acquired resistance to TNF after TNF-$\alpha$ cDNA transfection may not be associated with the change in the TNF receptor and the soluble TNF receptor expression.

• Clinical and Experimental Pediatrics
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• v.45 no.2
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• pp.240-246
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• 2002

Purpose : It is not clear that the development of glomerular injury and aggravation by tumor necrosis factor alpha($TNF-{\alpha}$) is related to intrarenal or serum concentration of $TNF-{\alpha}$. So, we studied the relationship between the concentration of $TNF-{\alpha}$ and aggravation of glomerular damage in the Henoch-$Sch{\ddot{o}}nlein$ nephritis(HSN) and idiopathic nephrotic syndrome(INS). Methods : We collected the sera and urines of 21 patients with Henoch-$Sch{\ddot{o}}nlein$ purpura(HSP) and 22 patients with INS visited Chungbuk National University hospital from March 1998 to March 2001. The concentration of $TNF-{\alpha}$ in the sera and urines were measured by sandwich ELISA. Results : Serum $TNF-{\alpha}$ levels in the HSP patients with renal involvement were significantly higher than those without renal involvement(P=0.009). But urine $TNF-{\alpha}$ levels have no correlation with renal involvement(P=0.088). In the HSN patients, proteinuria have a significant correlation with serum $TNF-{\alpha}$ levels(P=0.004) but less correlation with urine $TNF-{\alpha}$ levels(P=0.053). Otherwise, proteinuria have no correlation with serum $TNF-{\alpha}$ levels(P=0.763) but have a significant correlation with urine $TNF-{\alpha}$ levels(P=0.007) in INS. Conclusion : These result suggest that the serum concentration of $TNF-{\alpha}$ would be important to glomerular involvement in HSP. And, it is interesting that proteinuria shows a significant relation with serum $TNF-{\alpha}$ levels in the HSN, but with urine $TNF-{\alpha}$ levels in the INS. This means the major production of $TNF-{\alpha}$ may be originated by extrarenal inflammation in the HSN and by intrarenal tubulo-interstitial damage due to proteinuria in the INS.

• Journal of Life Science
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• v.18 no.9
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• pp.1207-1211
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• 2008

The pro-inflammatory cytokine tumor necrosis factor-$\alpha$ (TNF-$\alpha$) is an important mediator of the immune response in hepatitis B virus (HBV) infection. Since the production of TNF-$\alpha$ is mostly regulated at the transcriptional level and polymorphisms in the TNF-$\alpha$ promoter alter its expression, TNF-$\alpha$ promoter polymorphisms could affect the pathogenesis of chronic HBV infection. In this study, we investigated the potential association of TNF-$\alpha$ promoter polymorphisms with chronic HBV infection. The study included 181 patients with chronic HBV infection, 201 persons who had been spontaneously recovered from hepatitis B, and 170 unrelated healthy controls. The -308G/A and -238G/A polymorphisms in the TNF-$\alpha$ promoter were analyzed by PCR-restriction fragment length polymorphism. The distribution of both the -308 and -238 genotypes in the patient group was not statistically different from that in the spontaneous recovery and control groups (p>0.05). There was also no significant difference in the allele frequency between the groups (p>0.05). The results suggest that the TNF-$\alpha$ -308 and -238 promoter polymorphisms are not associated with the development of chronic HBV infection in the Korean population.

• The Journal of Korean Medicine
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• v.17 no.2 s.32
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• pp.227-236
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• 1996

The effect of Ligustrum Lucidum(LL) on the production of nitric oxide (NO) and superoxide by murine peritoneal macrophages were investigated. Stimulation of the cells with LL in the presence or absence of interferon-r(IFN-r) resulted in the increased accumulation of nitrite in the medium. To further examine the mechanism of LL induced. NO Synthesis, we evaluated the secretion of tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ by LL in murine macrophages. Treatment of LL increased the secretion of bioactive $TNF-{\alpha}$ in cultured medium. In addition, LL induced NO production was decreased by the treatment of anti-murine $TNF-{\alpha}$. neutralizing antibodies, indicating that LL induced superoxide production was decreased by the treatment of anti-murine $TNF-{\alpha}$ neutralizing antibodies. These data suggested that LL induced superoxide production was related to $TNF-{\alpha}$ secretion. In conclusion, our results indicates that LL may enhance innate immune response and be applied as a immunoregulating drug improving phagocytosis.