• IMMUNE NETWORK
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• v.13 no.5
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• pp.213-217
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• 2013

Enterotoxigenic Bacteroides fragilis (ETBF) is a human gut commensal bacteria that causes inflammatory diarrhea and colitis. ETBF also promotes colorectal tumorigenesis in the Min mouse model. The key virulence factor is a secreted metalloprotease called B. fragilis toxin (BFT). BFT induces E-cadherin cleavage, cell rounding, activation of the ${\beta}$-catenin pathway and secretion of IL-8 in colonic epithelial cells. However, the precise mechanism by which these processes occur and how these processes are interrelated is still unclear. E-cadherin form homophilic interactions which tethers adjacent cells. Loss of E-cadherin results in detachment of adjacent cells. Prior studies have suggested that BFT induces IL-8 expression by inducing E-cadherin cleavage; cells that do not express E-cadherin do not secrete IL-8 in response to BFT. In the current study, we found that HT29/C1cells treated with dilute trypsin solution induced E-cadherin degradation and IL-8 secretion, consistent with the hypothesis that E-cadherin cleavage causes IL-8 secretion. However, physical damage to the cell monolayer did not induce IL-8 secretion. We also show that EDTA-mediated disruption of E-cadherin interactions without E-cadherin degradation was sufficient to induce IL-8 secretion. Finally, we determined that HT29/C1 cells treated with LiCl (${\beta}$-catenin activator) induced IL-8 secretion in a dose-dependent and time-dependent manner. Taken together, our results suggest that BFT induced IL-8 secretion may occur by the following process: E-cadherin cleavage, disruption of cellular interactions, activation of the ${\beta}$-catenin pathway and IL-8 expression. However, we further propose that E-cadherin cleavage per se may not be required for BFT induced IL-8 secretion.

• The Korea Journal of Herbology
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• v.22 no.2
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• pp.25-33
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• 2007

Objectives : Oriental pear was used as treatment of asthma, control of blood pressure, diabetes in oriental medicine. The aim of this study was to observe the effects of Phenolic compound extracted from pear and herbal drugs to treat asthma. Methods : In order to study the effect of oral administration of phenolic compound extracted from pear and herbal drugs(Platycodon grandiflorum, Prunus armeniaca) on allergic asthma, mice were pre-treated by oral administration of the solution before antigen sensitization four times for 8 days. 2 days later, mice were actively sensitized with a subcutaneous injection of ovalbumin and 13 days later, they were provoked with ovalbumin aerosols. The animals were divided into four groups; Saline, orally administered saline. PC-A, orally administered Phenolic compound extracted from pear peel 10mg/kg/ml. PC-B, orally administered Phenolic compound extracted from pear peel and flesh 10mg/kg/ml. PC-C, orally administered pear 10m/kg/ml, Platycodon grandiflorum 24.4 mg/kg/ml and Prunus armeniaca 33.3 mg/kg/ml. Serum level of IgE, IL-4, cell numbers in the bronchoalveolar lavage fluid(BALF), and in vitro isometric contractile responses of the isolated tracheal smooth muscle(TSM) to acetylcholine(ACh, $0.1-1000{\mu}M$), KCl were measured. Results : Contractile responses of TSM to ACh were decreased in PC-A group at Ach 0.1, 0.3, 1 ${\mu}M$, decreased in PC-B at 0.1 ${\mu}M$ and decreased in PC-C at 0.1, 0.3, 1, 10, 30 ${\mu}M$. The maximal contractile response of TSM to KCl was decreased in PC-C group, The cell numbers of eosinophil in BALF were decreased in PC-C group, and those of macrophages in BALF were decreased in PC-A and PC-C group. Interleukin-4 in BALF was decreased in PC-A, PC-B, PC-C group. Conclusion : Based on the above results it is assumed that oral administration of phenolic compound extracted from pear and herbal drugs can help the treatment of deficiency allergic Asthma.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.2
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• pp.89-94
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• 2004

The arterial pressure is regulated by the nervous and humoral mechanisms. The neuronal regulation is mostly carried out by the autonomic nervous system through the rostral ventrolateral medulla (RVLM), a key area for the cardiovascular regulation, and the humoral regulation is mediated by a number of substances, including the angiotensin (Ang) II and vasopressin. Recent studies suggest that central interleukin-1 (IL-1) activates the sympathetic nervous system and produces hypertension. The present study was undertaken to elucidate whether IL-1 and Ang II interact in the regulation of cardiovascular responses to the stress of hemorrhage. Thus, Sprague-Dawley rats were anesthetized and both femoral arteries were cannulated for direct measurement of arterial pressure and heart rate (HR) and for inducing hemorrhage. A guide cannula was placed into the lateral ventricle for injection of IL-1 $(0.1,\;1,\;10,\;20\;ng/2\;{\mu}l)$ or Ang II $(600\;ng/10\;{\mu}l)$. A glass microelectrode was inserted into the RVLM to record the single unit spike potential. Barosensitive neurons were identified by an increased number of single unit spikes in RVLM following intravenous injection of nitroprusside. I.c.v. $IL-1\;{\beta}$ increased mean arterial pressure (MAP) in a dose-dependent fashion, but HR in a dose-independent pattern. The baroreceptor reflex sensitivity was not affected by i.c.v. $IL-1\;{\beta}$. Both i.c.v. $IL-1\;{\alpha}\;and\;{\beta}$ produced similar increase in MAP and HR. When hemorrhage was induced after i.c.v. injection of $IL-1\;{\beta}$, the magnitude of MAP fall was not different from the control. The $IL-1\;{\beta}$ group showed a smaller decrease in HR and a lower spike potential count in RVLM than the control. MAP fall in response to hemorrhage after i.c.v. injection of Ang II was not different from the control. When both IL-1 and Ang II were simultaneously injected i.c.v., however, MAP fall was significantly smaller than the control, and HR was increased rather than decreased. These data suggest that IL-1, a defense immune mediator, manifests a hypertensive action in the central nervous system and attenuates the hypotensive response to hemorrhage by interaction with Ang II.

• Journal of Pharmacopuncture
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• v.6 no.2
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• pp.7-27
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• 2003

Objective : The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with cultivated wild ginseng (distilled) in mice and rats. Method : Balb/c mice were injected intravenous with cultivated wild ginseng herbal acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were injected intravenous with cultivated wild ginseng herbal acupuncture for subacute toxicity test. The cultivated wild ginseng herbal-acupuncture was injected at the tail vein of mice. Results : 1. In acute $LD_{50}$ toxicity test, there was no mortality thus unable to attain the value. 2. Examining the toxic response in the acute toxicity test, there was no sign of toxication. 3. In acute toxic test, running biochemical serum test couldn't yield any differences between the control and experiment groups. 4. In subacute toxicity test, there was no sign of toxication in the experimental groups and didn't show any changes in weight compared to the normal group. 5. In subacute toxicity test, biochemical serum test showed significant increase of Total albumin, Albumin, and Glucose in the experimental group I compared with the control group. Significant decrease of GOT, ALP, GPT, and Triglyceride were shown. In experiment group II, only Glucose showed significant increase compared with the control group. 6. Measuring survival rate for anti-cancer effects of Sarcoma-180 cancer cell line, all the experimental groups showed significant increase in survival rate. 7. Measuring NK cell activity rate, no significant difference was shown throughout the groups. 8. Measuring Interleukin-2 productivity rate, all the experimental groups didn't show significant difference. 9. For manifestation of cytokine mRNA, significant decrease of interleukin-10 was witnessed in the experimental group compared to the control group. Conclusion : According to the results, we can conclude cultivated wild ginseng herbal acupuncture caused negligible toxicity, and had anti-tumor effects in mice.

• Clinical and Experimental Pediatrics
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• v.48 no.6
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• pp.634-639
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• 2005

Purpose : An understanding of the immunological process is required if primary prevention of atopic diseases is to be developed in early childhood. But, it is too hard to distinguish atopy from nonatopy under the age of two clinically, because the expression of phenotype and cytokines is vague in early childhood. We evaluated DNA methylation changes at Th2 interleukin-4 gene in peripheral blood from atopic children. Methods : We selected 15 allergic children(mild : eight, moderate to severe : seven) and seven normal controls by using family allergy scores and clinical histories. We measured Total IgE and Der f II specific IgE levels and cultured peripheral blood mononuclear cells with Der f II stimulation and extracted DNA from Der f II specific T cells. We examined the change of CpG methylation in DNA from atopic and nonatopic children. Results : In T cells from normal children, IL-4 DNA were predominantly methylated; otherwise, CpG demethylation occurred in Der f II specific T cells from allergic children. Conclusion : IL-4 DNA methylation changes occurred in T genes from allergic children and DNA methylation assay in early childhood.

• Journal of Microbiology and Biotechnology
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• v.24 no.8
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• pp.1133-1142
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• 2014

Interleukin-32 (IL-32) is a cytokine and inducer of various proinflammatory cytokines such as $TNF{\alpha}$, IL-$1{\beta}$, and IL-6 as well as chemokines. There are five splicing variants (${\alpha}$, ${\beta}$, ${\gamma}$, ${\delta}$, and ${\varepsilon}$) and IL-$32{\gamma}$ is the most active isoform. We generated human IL-$32{\gamma}$ transgenic (IL-$32{\gamma}$ TG) mice to express high level of IL-$32{\gamma}$ in various tissues, including immune cells. The pathology of sepsis is based on the systemic inflammatory response that is characterized by upregulating inflammatory cytokines in whole body, particularly in response to gram-negative bacteria. We investigated the role of IL-$32{\gamma}$ in a mouse model of experimental sepsis by using lipopolysaccharides (LPS). We found that IL-$32{\gamma}TG$ mice resisted LPS-induced lethal endotoxemia. IL-$32{\gamma}$ reduced systemic cytokines release after LPS administration but not the local immune response. IL-$32{\gamma}TG$ increased neutrophil influx into the initial foci of the primary injected site, and prolonged local cytokines and chemokines production. These results suggest that neutrophil recruitment in IL-$32{\gamma}TG$ occurred as a result of the local induction of chemokines but not the systemic inflammatory cytokine circulation. Together, our results suggest that IL-$32{\gamma}$ enhances an innate immune response against local infection but inhibits the spread of immune responses, leading to systemic immune disorder.

• Journal of Sasang Constitutional Medicine
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• v.12 no.1
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• pp.186-200
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• 2000

The purpose of this research was to investigate the effects of Indongdeungjikolpitang water extract(IJTE) on the complication of diabetes. IJTE did not affect the level of blood glucose in alloxan- or streptozotocin-induced hyperglycemic mice, but inhibited the motility of gastrointestine. IJTE inhibited the writhing syndrome induced by acetic acid, the permeability of evans blue into peritoneal cavity induced by acetic acid, the paw edema induced by histamine, and the formation of cotton pellet granuloma. IJTE increased the cell viability of thymocytes and splenocytes. IJTE decreased the release of ${\gamma}-interferone$(${\gamma}-IFN$) and interleukin-2(IL-2), but did not affect the release of interleukin-4(IL-4) from murine thymocytes. IJTE increased the release of IL-4 and decreased the release of tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$) and $interleukin-1{\beta}$($IL-1{\beta}$), but did not affect of ${\gamma}-IFN$ and IL-2 from murine splenocytes. IJTE decreased the release of $TNF-{\alpha}$ and $IL-1{\beta}$ from murine peritoneal macrophages. IJTE decreased the production of niric oxide(NO) from murine peritioneal macrophages and increased the phagocytic activity of murine peritoneal macrophages. These results suggest that IJTE has an anti-inflammatory action via the inhibition of $TNF-{\alpha}$, $IL-1{\beta}$ and NO production from immune cells.

• Journal of Chest Surgery
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• v.33 no.8
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• pp.648-654
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• 2000

Background: Cardiopulmonary bypass during open heart surgery causes systemic inflammatory respose. IL-10 is an anti-inflammatory cytokine that inhibits inflammatory process and protects organ function by down regulation of pro-inflammatory cytokine release and maintenance of blood level balance with pro-inflammatory cytokines. Mateial and Method: Plasma IL-10 levels were measured and analyzed in 22 patients who underwent open heart surgery (11 cases of coronary artery bypass graft, 11 cases of valve replacement) under cardiopulmonary bypass since 1988 January to July at Department of Thoracic and Czardiovascular surgery, Yeungnam University Hospital. 1g of methylprednisolone was administrated to thirteen patients randomly. Blood samp.es were taken and collected at the time of induction of anesthesia, 10 min before cardiopulmonary bypass, 10 min after starting of CPB, 10 min aftr aortic cross clamping, 10 min after ACC release, and 10 min, 2 hours, and `5 hours after CPB respectively. The plasma levels of IL-10 were determined by enzyme-linked immunosorbent assays(ELISA). Wilcoxon-Raule Sum test was used for statistical analysis. Result: In all 22 patients, cardiopulmonary bypass time was used for statistical analysis. Result: In all 22 patients, cardiopulmonary bypass time was 171$\pm$41.4 min and aortic cross clamp time was 118$\pm$36.5 min. Peak IL-10 level was achieved at 10 min after ACC(361.0$\pm$52.81pg/ml) and was decreased sharply at 2 hours after CPB. Peak IL-10 level was correlated positively with aortic cross clamp time(p=0.011); however, it did not correlated with bypass time(p=0.181). In valve replacement group, mean IL-10 level at peak point was 567.89$\pm$107.69 pg/ml and was significantly higher than that of coronary artery bypass group(205.67$\pm$192.70 pg/ml)(p<0.001). ACC time in valve replacement group was significantly longer than that of coronary artery bypass group(p<0.01), however, bypass time was not(p=0.212). Thirteen patients with steroid pretreatment before starting of CPB showed relatively higher plasma IL-10 level than in control group, however, no statistical significance was noted(p=0.19). Conclusion: plasma level of IL-10 was increased in association with cardiopulmonary bypass and revealed peak at 10 min after ACC release. IL-10 level was correlated positively with ACC time. Therefore, systemic inflammatory respeonse in association with cardiopulmonary bypass could be decreased by reducing ACC time during cardiac surgery.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.7
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• pp.912-919
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• 2017

Objective: Identification of the candidate genes that play key roles in phenotypic variations can provide new information about evolution and positive selection. Interleukin (IL)-32 is involved in many biological processes, however, its role for the immune response against various diseases in mammals is poorly understood. Therefore, the current investigation was performed for the better understanding of the molecular evolution and the positive selection of single nucleotide polymorphisms in IL-32 gene. Methods: By using fixation index ($F_{ST}$) based method, IL-32 (9375) gene was found to be outlier and under significant positive selection with the provisional combined allocation of mean heterozygosity and $F_{ST}$. Using nucleotide sequences of 11 mammalian species from National Center for Biotechnology Information database, the evolutionary selection of IL-32 gene was determined using Maximum likelihood model method, through four models (M1a, M2a, M7, and M8) in Codeml program of phylogenetic analysis by maximum liklihood. Results: IL-32 is detected under positive selection using the $F_{ST}$ simulations method. The phylogenetic tree revealed that goat IL-32 was in close resemblance with sheep IL-32. The coding nucleotide sequences were compared among 11 species and it was found that the goat IL-32 gene shared identity with sheep (96.54%), bison (91.97%), camel (58.39%), cat (56.59%), buffalo (56.50%), human (56.13%), dog (50.97%), horse (54.04%), and rabbit (53.41%) respectively. Conclusion: This study provides evidence for IL-32 gene as under significant positive selection in goat.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.1-12
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• 2005

Objective: With the onset of stroke, white blood cells release several proinflammatory cytokines, including interleukin (IL)-6, IL-10, and tumor necrosis factor $(TNF)-{\alpha}$. It has been proven in previous studies that the release of these cytokines is related to the extent of damage to the brain and to overall prognosis. However, no studies have yet been performed to determine the connection with IL-6 and IL-10. Thus, this study is performed to see whether polymorphisms of IL-6, IL-10, and $TNF-{\alpha}$ genes that show increased serum concentration with the onset of stroke are related to stroke attack in Koreans. Methods : Peripheral blood samples derived from patients with stroke (n=100) and healthy controls (n=100) were taken under informed consent. In subjects with stroke, blood samples were obtained within 24 hours of stroke onset. Genomic DNA was isolated using the Wizard DNA Purification Kit (Promega, Madison, WI). Results : 1. Subjects with Heterozygote (GA) and Homozygote (AA) $TNF-{\alpha}$ gene types showed 2.433 and 20.457 times higher risks of being attacked by stroke, respectively, compared to subjects with wild type (GG) $TNF-{\alpha}$ gene type. The data was still statistically significant after adjusting for age, sex, history of smoking, and history of alcohol drinking. 2. Subjects with Homozygote (CC) IL-6 gene type showed 182.033 times higher risk of being attacked by stroke, compared to subjects with wild type (GG) IL-6 genes. This data was statistically insignificant (p=0.700). The data was still statistically insignificant after adjusting for age, sex, history of smoking, and history of alcohol drinking. 3. Subjects with Heterozygote (GA) and Homozygote (GG) IL-10 gene types showed 8.785 and 3.303 times higher risks of being attacked by stroke, respectively, compared to subjects with wild type (AA) IL-10 genes. The data was still statistically insignificant after adjusting for age, sex, history of smoking, and history of alcohol drinking. Conclusion : Our results suggest that the investigated $TNF-{\alpha}$ and IL-10 gene polymorphisms play an important role in stroke attack, but IL-6 gene polymorphism has not been found to associated with stroke.