• Journal of Veterinary Clinics
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• v.17 no.2
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• pp.311-315
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• 2000

Recombinant interleukin-2 (IL-2) has been demonstated as an antineoplastic agent in mice and human, and the route of administration is important to IL-2-induced therapeutic responses. Therefore, the current experiment was undertaken to clarify the effect of IL-2 administration route on antitumor response against subcutaneous Meth-A tumor in mice. At the beginning of each experiment, normal BALB/c mice were injected subcutaneously with $5{\times}10^6$ Meth-A tumor cells. Beginning on day 7, experimental groups were treated with a 5-day course of IL-2 (intraperitoneal or subcutaneous injection of 30, 000 IU every 12 hours for 5 days). The result of this experiment revealed that Meth-A tumor grew progressively in control mice. Intraperitoneal IL-2 treatment decreased significantly tumor growth and prolonged survival, compared with control mice. Subcutaneous IL-2 treatment decreased significantly tumor growth until day 11 and tumor cells, grew progressively thereafter, but mice in this group survived longer than control mice.

• Korean Journal of Veterinary Service
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• v.25 no.3
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• pp.309-314
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• 2002

Recombinant interleukin-2(IL-2) has demonstrated as an antineoplastic agent in mice and human, but the relatively low response rates observed in clinical trials. Therefore, the present study was undertaken in order to evaluate therapeutic activities of IL-2 for the establishment of therapeutic applications. At the onset of the experiment, normal C3H/HeN mice were injected with 5$\times$10$\^$6/ RD-995 tumor cells, murine ultraviolet radiation-induced fibrosarcoma, intraperitoneally. Beginning on day 6, experimental groups were treated with a 5-day course of IL-2(subcutaneous injection of 30,000 IU every 12 hours for 5 days). The result of this experiment revealed that body weight gradually decreased from 20th day in control mice. Subcutaneous IL-2 therapy prevented partially decrease body weight, and prolonged survival of mice compared with control group.

• Korean Journal of Veterinary Research
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• v.56 no.3
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• pp.183-187
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• 2016

The effects of antlers have long been known in traditional Asian medicine. However, few studies have investigated the effects of antlers on immunity. In this study, we investigated whether fermented antler extract (FAE) has immunomodulatory effects on spleen cells. FAE enhanced the activity of spleen cells in a concentration dependent manner compared to antler extract. Interestingly, FAE significantly increased the production of interleukin-12, a representative cytokine of cell-mediated immunity, while it marginally increased that of tumor necrosis factor-alpha. Flow cytometry analysis demonstrated that FAE can protect spleen cells from spontaneous cell death without a significant proportional change in subsets, mainly lymphocytes. Taken together, the results of the present study showed that FAE has beneficial effects on spleen cells, a major type of immune cell, indicating that it can function as an immunomodulator without significant cytotoxicity. These data may broaden the use of FAE in basic research and clinical areas.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.471-479
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• 2023

Disulfiram (DSF), a medication for alcoholism, has recently been used as a repurposing drug owing to its anticancer effects. Despite the crucial role of dendritic cells (DCs) in immune homeostasis and cancer therapy, the effects of DSF on the survival and function of DCs have not yet been studied. Therefore, we treated bone marrow-derived DCs with DSF and lipopolysaccharide (LPS) and performed various analyses. DCs are resistant to DSF and less cytotoxic than bone marrow cells and spleen cells. The viability and metabolic activity of DCs hardly decreased after treatment with DSF in the absence or presence of LPS. DSF did not alter the expression of surface markers (MHC II, CD86, CD40, and CD54), antigen uptake capability, or the antigen-presenting ability of LPS-treated DCs. DSF decreased the production of interleukin (IL)-12/23 (p40), but not IL-6 or tumor necrosis factor-α, in LPS-treated DCs. We considered the granulocyte-macrophage colony-stimulating factor (GM-CSF) as a factor to make DCs resistant to DSF-induced cytotoxicity. The resistance of DCs to DSF decreased when GM-CSF was not given or its signaling was inhibited. Also, GM-CSF upregulated the expression of a transcription factor XBP-1 which is essential for DCs' survival. This study demonstrated for the first time that DSF did not alter the function of DCs, had low cytotoxicity, and induced differential cytokine production.

• Korean Journal of Acupuncture
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• v.26 no.3
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• pp.43-54
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• 2009

Objectives : To investigate the anti-inflammatory effects of Prunella vulgaris pharmacopuncture in lipopolysaccharide (LPS)-induced inflammatory rat model. Methods : Sprague-Dawley rats were divided into 5 groups; normal control (n=8), LPS control (n=8), LPS+Prunella vulgaris pharmacopuncture at CV4 (CV4, n=8), LPS+Prunella vulgaris pharmacopuncture at ST36 (ST36, n=8), and LPS+Prunella vulgaris pharmacopuncture at CV12 (CV12, n=8). Pharmacopuncture was given every two days for 4 weeks followed by inflammation induction by peritoneal LPS injection (5mg/kg). Proinflammatory cytokines including interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6), tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-10 (IL-10), thiobarbituric acid reactive substance (TBARS) from blood and liver tissue were compared before and 5 hrs after inflammation induction. Results : In CV4 and CV12 groups, plasma IL-$1{\beta}$, IL-6 and TNF-$\alpha$ levels increased by LPS injection, significantly decreased 5 hrs after injection (p<0.05). For CV12 group, plasma IL-10 concentration significantly increased (p<0.05). Liver IL-$1{\beta}$ and IL-6 levles significantly decreased in CV4 and CV12 groups (P<0.05), while normal and LPS control groups were not significantly different in TNF-$\alpha$ and IL-10 levels. Plasma TBARS concentration was significantly decreased in CV12 group, while there was no significant difference among LPS control and pharmacopuncture groups for liver TBARS concentration. Conclusions : Based on the present findings, Prunella vulgaris pharmacopuncture at CV12 may have a potentially preventive anti-inflammatory effect in an LPS-induced inflammatory rat model.

• Archives of Pharmacal Research
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• v.20 no.5
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• pp.396-403
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• 1997

In order to direct the form of the immune response in an antigen-specific manner, we constructed a fusion protein (OVA/IL12) that contained the T cell-dependent antigen, ovalbumin (OVA), covalently linked to murine interleukin-12 (IL-12). The OVA/IL12 protein was produced in a baculovirus expression system and was purified by anti-OVA immunoaffinity chromatography. The purified OVA/ILI2 protein displayed potent IL-12 bioactivity in an IL-12 proliferation assay. BALB/c mice immunized with the OVA/IL12 protein produced increased quantities of anti-OVA IgG2a antibody compared with mice immunized with recombinant OVA alone. Lymph node cells from the immunized mice with the OVA/IL12 protein produced large amounts of IFN-,Y when restimulated in vitro with OVA, while those from mice immunized with the OVA protein produced little or no IFN-.gamma.. In contrast, immunization with a mixture of OVA and free recombinant IL-12 also induced IFN-.gamma. production, which was not OVA-specific. These studies indicate that the OVA/IL12 fusion protein can induce OVA-specific, Th1-dominated immune responses, and that the covalent linkage of OVA and IL-12 confines the effect of IL-12 to OVA-specific cells.

• Journal of Gastric Cancer
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• v.4 no.3
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• pp.149-155
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• 2004

Purpose: According to the recent studies, it is shown that the polymorphism of Interleukin $1\beta$ gene is associated with the incidence of gastric cancer caused by the Helicobacter pylori infection. Interleukin $1\beta$ is a cytokine markedly inhibiting gastric acid secretion. Interleukin $1\beta$ production associated with Helicobacter pylori gastric infection may exacerbate mucosal damage including chronic gastritis and atrophic gastritis, may induce eventual neoplasia. Among these Interleukin $1\beta$ gene polymorphisms, polymorphisms at -31 portion and -511 portion may associated with these processes, eventually increase the risk of gastric cancer. We investigated the risk of gastric cancer according to the Helicobacter pylori infection and genetic polymorphism of Interleukin $1\beta$ in gastric cancer patients. Materials and Methods: 176 individuals with gastric cancer and 40 healthy controls were analyzed. Each group was divided into two groups whether they infected with Helicobacter pylori or not. DNA was extracted from the peripheral blood in all groups. The PCR-RFLP method was used for investigating the distribution of genotype of C/C, C/T, T/T at -31 portion and -511 portion. Results: T/T genotype at -511 portion was $19.3\%$ in gastric cancer cases and $10\%$ in controls, which was statistically significant. (P=0.0432) The risk of gastric cancer was increased 4.86 ($1.26\∼18.77$) in group which had T/T genotype. In gastric cancer cases, C/C genotype at 31 portion was $27.6\%$ in group with Helicobacter pylori infection and $12.8\%$ in group without infection, which was statistically significant. (P=0.0047) The risk of gastric cancer was increased 4.82 ($1.81\~12.81$) in group which had C/C genotype. Conclusion: T genotype at -511 portion among the Interleukin $1\beta$ genetic polymorphisms may be the risk factor of gastric cancer. And, with Helicobacter pylori infection, C genotype at -31 portion may be the risk factor of gastric cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.5
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• pp.426-429
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• 2006

The fibroblast in the periodontal ligaments received various stress. Among them, compression and tension are quite important and they are related to the remodeling of tooth and alveolar bone. We studied the change of expression of interleukin-6 (IL-6) and interleukin-8 (IL-8) in the fibroblasts of the periodontal ligaments by real-time RT-PCR and ELISA. In results, the relative activity of IL-6 mRNA in 2 hours after was 1.54${\pm}$0.08 and 1.00${\pm}$0.05 in control and test, respectively (P<0.05). Its 12 hours after was 1.23${\pm}$0.06 and 2.78${\pm}$0.14 in control and test, respectively (P<0.05). The relative activity of IL-8 mRNA in 2 hours after was 1.00${\pm}$0.05 and 0.24${\pm}$0.01 in control and test, respectively (P<0.05). Its 12 hours after was 1.23${\pm}$0.06 and 0.63${\pm}$0.03 in control and test, respectively (P<0.05). The concentration of IL-6 was 1.02${\pm}$0.16 ng/ml, 0.90${\pm}$0.14 ng/ml, and 1.32${\pm}$0.12 ng/ml (P<0.05) in control, 2, and 12 hours after, respectively. The concentration of IL-8 was 2.26${\pm}$0.17 ng/ml, 1.70${\pm}$0.26 ng/ml (P<0.05), and 0.84${\pm}$0.47 ng/ml (P<0.05) in control, 2, and 12 hours after, respectively. In conclusion, the expression of IL-6 was significantly increased after the application of the static compressive force, but IL-8 was significantly decreased. Considering their known function, their expression is quite important in tooth and bone resorption.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7869-7873
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• 2014

Interleukin-12 (IL-12) as an antitumor and interleukin-6 (IL-6) as an inflammatory cytokine, are immunomodulatory products that play important roles in responses in cancers and inflammation. We tested the association between two polymorphisms of IL-12(1188A>C; rs3212227) and IL-6 (-174 C>G) and the risk of bladder cancer in 261 patients and 251 healthy individuals. We also investigated the possible association of these SNPs in patients with high-risk jobs and smoking habits with the incidence of bladder cancer. The genotype distributions of IL-6 (-174 C/G) genotype were similar between the cases and the control groups; however, among patients with smoking habits, the association between IL-6 gene polymorphism and incidence of bladder cancer was significant. After a control adjustment for age and sex, the following results were recorded: CC genotype (OR= 2.11, 95%CI=1.56-2.87, p=0.007), GC genotype (OR=2.18, 95%CI=1.16-4.12, p=0.014) and GC+CC (OR=2.6, 95%CI=1.43-4.47, p=0.011). A significant risk of bladder cancer was observed for the heterozygous genotype (AC) of IL-12 (OR=1.47, 95%CI=1.01-2.14, p=0.045) in all cases, and among smokers (AC) (OR=3.13, 95%CI=1.82-5.37, p=0.00014), combined AC+CC (OR=3.05, 95%CI=1.8-5.18, p=0.000015). Moreover among high risk job patients, there was more than a 3-fold increased risk of cancer in the carriers of IL-12 beta heterozygous (OR=3.7, 95%CI=2.04-6.57, p=0.000056) and combined AC+CC(OR=3.29, 95%CI=1.58-5.86, p=0.00002) genotypes as compared with the AA genotype with low-risk jobs. As a conclusion, this study suggests that IL-12(3'UTR A>C) and IL-6 (-174 C>G) genotypes are significantly associated with an increased risk of bladder cancer in the Iranian population with smoking habits and/or performing high-risk jobs.

• BMB Reports
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• v.49 no.12
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• pp.693-698
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• 2016

In this study, a tissue-specific GAL4/UAS activation tagging system was used for the characterization of genes which could induce lethality when ubiquitously expressed. A dominant mutant exhibiting stunted growth was isolated and named defective root development 1-D (drd1-D). The T-DNA tag was located within the promoter region of AtTX12, which is predicted to encode a truncated nucleotide-binding leucine-rich repeat (NLR) protein, containing a Toll/interleukin-1 receptor (TIR) domain. The transcript levels of AtTX12 and defense-related genes were elevated in drd1-D, and the misexpression of AtTX12 recapitulated the drd1-D phenotypes. In the presence of ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1), a key transducer of signals triggered by TIR-type NLRs, a low-level of AtTX12 misexpression induced strong defective phenotypes including seedling lethality whereas, in the absence of EDS1, a high-level of AtTX12 misexpression induced weak growth defects like dwarfism, suggesting that AtTX12 might function mainly in an EDS1-dependent and partially in an EDS1-independent manner.