• BMB Reports
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• v.39 no.1
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• pp.1-8
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• 2006

Helicobacter pylori is the definitive carcinogen for stomach cancer and is known to induce proinflammatory cytokines, such as tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1(IL-1) in the stomach. Based on our findings that TNF-$\alpha$ is an endogenous tumor promoter, we identified the TNF-$\alpha$ inducing protein (Tip$\alpha$) gene family, and confirmed Tip$\alpha$ and HP-MP1 as new carcinogenic proteins of H. pylori. Tip$\alpha$ protein is unique to H. pylori, and this paper shows the strong tumor promoting activity of Tip$\alpha$ gene family, in cooperation with Ras protein and its mechanisms of action in relation to NF-${\kappa}B$ activation, and discusses the carcinogenic role of Tip$\alpha$ in stomach cancer. Our recent finding showing that penicillin-binding proteins of other bacteria are weak homologues of Tip$\alpha$ is also discussed.

• Journal of Acupuncture Research
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• v.20 no.5
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• pp.50-62
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• 2003

Objective: Bee Venom(BV) has been used for various kinds of inflammatory or painful conditions in Oriental Medicine clinics, and there publishes reports on its therapeutic effects and the probable mechanism of those therapeutic effects, where CDs and cytokines plays important role. This study investigated the influences of bee venom on the expressions of CDs and cytokines of HMC cell line Methods: In this study we analysed the expression profile of HMC cell line treated with BV of 10-2ug/ml in relation to that of HMC cell line treated with vehicle by way of CD/cytokine microarray hybridization with 342 genes on it. Results: There were no upregulated genes by more than 3 fold, while there showed some downregulated genes by less than 1/3 fold as follows: colony stimulating factor 2, CD122, IL-7, CD112, TNF-alpha, CD138, CD166, TGFbetaR2, CD42b, CD62L, CD111, interleukin 10 receptor alpha, colony stimulating factor 1(macrophage), CD38 antigen(p45), CD121a, CD33 antigen(gp67), colony stimulating factor 1 receptor, B cell linker protein (SLP65) mRNA, CD94, alanyl(membrane) aminopeptidase, immunoglobulin(CD79A) binding protein 1, CD205, CD241, CD207, CDw121b, integrin alpha L(CD11a), integrin beta 1(CD29), CD91, CD42b. Conclusions: Bee venom treatment induced downregulation of some CDs or cytokines including $TNF-{\alpha}$. IL-1R with its possible implication in an antiinflammatory action of BV. Further research on expression profile changes induced by BV treatment is expected.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.5
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• pp.370-378
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• 2005

The purpose of this study is that evaluate the distribution and biological roles of TNF-a, interleukin-1${\beta}$(IL-1${\beta}$), interleukin-6(IL-6) and tissue inhibitors of metalloproteinase-1(TIMP-1) in the synovial fliud of patients with non-inflammatory chronic temporomandibular joint(TMJ) disorders in relation to pain during joint movements and magnetic resonance imaging(MRI) findings. TMJ synovial fluids aspirates were obtained from 36 patients (36 joints) with chronic TMJ disorders and from 8 controls(8 joints). Patients were divided to four groups. The control group was from healthy volunteers(8 joints), group I(18 joints) was patients with anterior disc displacement with reduction, group II(5 joints) was patients with disc displacement without reduction and group III (5 joints) was osteoarthritis. The TNF-${\alpha}$, IL-1${\beta}$ and IL-6 levels in the aspirates were determined by using an enzyme-linked immunosorbent assay and the TIMP-1 level was measured by an enzyme immunoassay. Following examinations for pain during joint movements and MRI observations, these cytokines' level and frequencies of detection were compared. The level of IL-1${\beta}$was not significant different in all groups. but the level of TNF-${\alpha}$, IL-6 and TIMP-1 were significant different among groups. The level of IL-6 and TIMP-1 were correlated to pain during movement(p<0.01) and the level of TNF-a(p<0.05). Also, the level of IL-6 was correlated to the level of TIMP-1(p<0.01). Especially, The level of the TIMP-1 level was significantly correlated to the pain during movement and showed very high levle of Pearson's correlation coefficient (r=0.833)(p<0.001). The results indicated that the TNF-${\alpha}$, IL-6 and TIMP-1 levels in the TMJ aspirates of patients with chronic TMJ disorders have been raised. Especially, IL-6 and TIMP-1 were very high levels in the patients who were degraded in the TMJ. Also, TNF-${\alpha}$, IL-6 and TIMP-1 showed the significant correlation in the chronic temporomandibular joint disorders. Therefore I suggest that these cytokines were also correlated to the pain during movement in the chronic temporomandibular joint disorders.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.1
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• pp.35-46
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• 2011

Objectives : The present study investigated inflammatory effect of Rheum undulatum L. in lipopolysaccharide-exposed rats and Raw 264.7 cells. Methods : Male rats weighting $185.39{\pm}8.21g$ fed basal diet for 1 week and 32 rats were divided into a control group and 3 experimental groups. We fed a control group of rats a basal diet and administered normal saline(100 mg/kg, 1time/1day) for 6 weeks. And we fed basal diet and administered an extract of Rheum undulatum L.(100 mg/kg, 200 mg/kg, 300 mg/kg, 1time/1day) to each experimental group of rats. We measured the plasma concentration of $IL-1{\beta}$($interleukin-1{\beta}$), IL-6 and $TNF-{\alpha}$(tumor necrosis $factor-{\alpha}$), liver cytokines, Raw 264.7 macrophages cytokines. Results : The plasma concentration of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ peaked at 5h(hour) after LPS(lipopolysaccharides) injection, and the values of the Rheum undulatum L. extract groups were lower than those of the control group. In the increment of these cytokines concentration at 2h and 5h after LPS injection, the Rheum undulatum L. groups were lower than that of control group. The plasma concentration of IL-10 peaked at 5h after LPS injection, and the values of the Rheum undulatum L. extract groups were higher than those of the control group. In the increment of this cytokine concentration at 2h and 5h after LPS injection, the Rheum undulatum L. groups were higher than that of control group. Liver cytokines measurement was done at 5h after LPS injection. The concentration of liver $IL-1{\beta}$ and IL-6 in the Rheum undulatum L. groups was lower than that of the control group. The concentrations of liver $TNF-{\alpha}$, and IL-10 showed no significant differences among all the treatment groups. In the studies of lipopolysaccharide-exposed Raw 264.7 cells, the concentration of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ in the lipopolysaccharide-exposed cells groups was higher than that of control group(normal group), and in the lipopolysaccharide-exposed cells groups, these values showed a tendency to decrease in the Rheum undulatum L. groups. The concentration of IL-10 in the lipopolysaccharide-exposed cells groups was higher than that of control group(normal group), and in the lipopolysaccharide-exposed cells groups, the values showed a tendency to increase in the Rheum undulatum L. groups. Conclusions : These results indicate that the Rheum undulatum L. extracts have an functional material for inflammatory activities.

• Natural Product Sciences
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• v.25 no.3
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• pp.215-221
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• 2019

Inflammation is the crucial biological process of immune system which acts as body's defense and protective response against the injuries or infection. However, the systemic inflammation devotes the adverse effects such as multiple inflammation associated diseases. One of the best ways to treat this entity is by blocking the tumor necrosis factor alpha ($TNF-{\alpha}$) and TNF-related apoptosis-inducing ligand (TRAIL) to avoid the proinflammation cytokines production. Thus, this study aims to evaluate the potency of Sambucus bioactive compounds as anti-inflammation through in silico approach. In order to assess that, molecular docking was performed to evaluate the interaction properties between the $TNF-{\alpha}$ or TRAIL with the ligands. The 2D structure of ligands were retrieved online via PubChem and the 3D protein modeling was done by using SWISS Model. The prediction results of the study showed that caffeic acid (-6.4 kcal/mol) and homovanillic acid (-6.6 kcal/mol) have the greatest binding affinity against the $TNF-{\alpha}$ and TRAIL respectively. This evidence suggests that caffeic acid and homovanillic acid may potent as anti-inflammatory agent against the inflammation associated diseases. Finally, this study needs further examination and evaluation to validate the potency of Sambucus bioactive compounds.

• 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.

• The Journal of Pediatrics of Korean Medicine
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• v.28 no.3
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• pp.31-46
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• 2014

Objectives Forsythiae Fructus treatment has been used for inflammatory and allergic diseases in Korean Medicine. Nevertheless, the mechanism of action and the cellular targets are not understood well. The pathogenesis of allergic diseases are associated with Th2 cytokines such as IL-13, MIP-$1{\alpha}$, IL-13, IL-5, GM-CSF, IL-4, TNF-${\alpha}$ and IL-6, which are secreted by the mast cells. This study was conducted to investigate the effects of Forsythiae Fructus extracts (FF) on Th2 cytokines expression and signal transduction in MC/9 mast cells. Methods In the study, MC/9 mast cells were stimulated with DNP-IgE for 24 hours and then treated separately with CsA $10{\mu}g/m{\ell}$ and varying doses of FF for one hour. MC/9 mast cells stimulated with DNP-IgE was the control group, a treatment with CsA was the positive control group and a treatment with varying doses FF was the experimental groups. The mRNA levels of IL-13, IL-5, GM-CSF, IL-4, TNF-${\alpha}$, IL-6 were analyzed with Real-time PCR. The levels of IL-13, MIP-$1{\alpha}$ were measured using enzyme-linked immunosorbent assays(ELISA). NFAT, AP-1 and NF-${\kappa}B$ p65 were examined by Western blot analysis. Results 1. FF were observed to suppress the mRNA expression of IL-13, IL-5, GM-CSF, IL-4, TNF-${\alpha}$, IL-6 in comparison to DNP-IgE control group. 2. FF also has inhibited the IL-13, MIP-$1{\alpha}$ production significantly in comparison to DNP-IgE control group. 3. Western blot analysis of transduction factors involving Th2 cytokines expression has revealed a prominent decrease of the mast cell specific transduction factors including NFAT-1, NFAT-2, c-Jun, and NF-${\kappa}B$ p65 but c-Fos. Conclusions In conclusion, the anti-allergenic activities of FF may be strongly related to the regulation of transcription factors NFAT-1, NFAT-2, c-Jun, and NF-${\kappa}B$ p65 causing inhibition of Th2 cytokines in mast cells.

• The Journal of Pediatrics of Korean Medicine
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• v.28 no.2
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• pp.23-39
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• 2014

Objectives PRAL (Prunus armniaca Linne Var) is a herbal formula in Oriental Medicine, known for its anti-inflammatory and anti-allergenic properties. However, its mechanism of action and the cellular targets have not yet been found enough. The purpose of this study is to investigate the effects of PRAL on Th2 cytokines expression in MC/9 mast cells. Methods The effect of PRAL was analyzed by ELISA, Real-time PCR, Western blot in MC/9 mast cells. mRNA levels of GM-CSF, IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ were analyzed with Real-time PCR. Levels of IL-13, MIP-$1{\alpha}$ were measured using enzyme-linked immunosorbent assays (ELISA). NFAT, AP-1 and NF-${\kappa}B$ p65 were examined by Western blot analysis. Results PRAL inhibited GM-CSF, IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ mRNA expression in a dose dependent manner. GM-CSF, IL-4, IL-5 mRNA expression were inhibited significantly in comparison to DNP-IgE control group at concentration of 100 ${\mu}g/ml$ and IL-6, IL-13, TNF-${\alpha}$ mRNA expression were inhibited at concentration of 50 ${\mu}g/ml$, 100 ${\mu}g/ml$. PRAL also inhibited the IL-13, MIP-$1{\alpha}$ production significantly in comparison to DNP-IgE control group in a dose dependent manner. IL-13 production was inhibited at a concentration of 200 ${\mu}g/ml$, 400 ${\mu}g/ml$ and MIP-$1{\alpha}$ was inhibited at a concentration of 100 ${\mu}g/ml$, 200 ${\mu}g/ml$, 400 ${\mu}g/ml$. Western blot analysis of transcription factors involving Th2 cytokines expression revealed prominent decrease of the mast cell specific transcription factors including NFAT-1, c-Jun as well as NF-${\kappa}B$ p65 but not NFAT-2 and c-Fos. Conclusion These results indicate that PRAL has the effect of suppressing Th2 cytokines production in the MC/9 mast cells. These data represent that PRAL potentiates therapeutic activities to the allergic disease by regulating Th2 cytokines in the MC/9 mast cells.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.6
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• pp.315-322
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• 2005

In this study, the authors investigated whether death of vascular smooth muscle cell (VSMC) had a pathological pertinence. Conditioned media obtained from rat aorta smooth muscle cell (SMC) that were induced death by expressing FADD in the absence of tetracycline (FADD-SMC) triggered death of normal SMC. DNA fragmentation and caspase-3 activation were observed in dying SMC by conditioned media. FADD-SMC showed transcriptional activation of tumor necrosis factor $(TNF)-{\alpha}$. Conditioned medium contained $TNF-{\alpha}$, indicating secretion of the cytokine from dying FADD-SMC. It was investigated if secreted $TNF-{\alpha}$ was functional. Conditioned medium activated ERK and p38 MAPK pathways and induced MMP-9 expression, whereas depletion of the cytokine with its soluble receptor (sTNFR) remarkably inhibited induction of MMP-9 by conditioned medium. These findings suggest that $TNF-{\alpha}$ in conditioned medium seems to be active. Then, contribution of $TNF-{\alpha}$ on death-inducing activity of conditioned medium was examined. Depletion of $TNF-{\alpha}$ with soluble $TNF-{\alpha}$ receptor decreased the death activity of conditioned medium by 35%, suggesting that $TNF-{\alpha}$ play a partial role in the death activity. Boiling of medium almost completely abolished the death-inducing activity, suggesting that other heat labile death inducing proteins existed in conditioned medium. Taken together, these results indicate that SMC undergoing death could contribute to inflammation by expressing inflammatory cytokines and pathological complications by inducing death of neighboring cells.

• Journal of Lipid and Atherosclerosis
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• v.7 no.2
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• pp.98-109
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• 2018

Objective: To examine the effects of sodium intake on the correlations between the saltsensitive gene ${\alpha}$-adducin 1 (ADD1) and inflammatory cytokines in Korean childhood obesity. Methods: A total of 2,070 students aged 8-9 years old participated in this study. The anthropometrics, serum biochemistry profile, inflammatory cytokines, and three-day dietary assessment were analyzed according to sex, obesity degree, and ADD1 polymorphism. Results: The obesity prevalence was higher in boys (15.6%) than in girls (11.9%). Boys also showed higher values in anthropometrics; lipid, glucose, and insulin profiles; total calorie intakes, as well as those of sodium and calcium compared with those of the girls. The more obese were boys and girls, the higher were the anthropometrics and the blood levels (total cholesterol, triglyceride, low-density lipoprotein cholesterol, fasting blood sugar, and insulin), but the lower was high-density lipoprotein cholesterol. The obese boys had significantly higher sodium and Na/K intakes, while the obese girls had higher visfatin level and Na/K intake. In addition, an increase in the risk factors for blood pressure and obesity in ADD1 variants was identified. Serum tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$) significantly increased with increasing sodium intake in the ADD1 W allele carriers, regardless of sex. The presence of obesity with the ADD1 W allele induced inflammatory accelerators such as $TNF-{\alpha}$ or C-reactive protein(CRP) with higher sodium intake. Conclusion: Obese children with an ADD1w allele can experience a more complex form of obesity than non-obese when exposed to an obesity-inducing environment and need to be controlled sodium intake in the diet.