• Journal of Pharmacopuncture
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• v.9 no.3 s.21
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• pp.23-35
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• 2006

Objectives : The aim of this study was to investigate the effect of Asthma-depression and Immunoregulation with PR-HAS(Herbal-acupuncture with Platycodi Radix infusion solution) infection at Joksamni(St36) on ovalbumin-induced asthma in mice. Methods : C57BL/6 mice were sensitized and challenged with OVA(ovalbumin) for 12 weeks(once a week). The experimental group(OVA-PR-HA) was treated with concentrations(1%) of PR-HAS at Joksamni(St36) for the later 8 weeks(3times/week). The second experimental group(OVA-Needle prick) was treated with Needle-Prick at Joksamni(St36) for the later 8 weeks(3times/week). Results : 1. The weight and total cells in the mice lung treated with PR-HA decreased significantly compared with that of control group. 2. Total leukocytes and eosinophils in BALF of the mice group treated with PR-HA decreased remarkably compared with those of control group. 3. The sticking of collagen on histological analysis of lung sections, the mice group treated with PR-HA decreased significantly compared with those of control group. 4. The concentrations of IL-4, IL-5, IgE in BALF, and IL-4, IL-5, IL-13 in serum of the mice group treated with PR-HA decreased significantly compared with those of control group. 5. The number of Gr-1+/CD11b+ and CD11b+ cells in the lungs of the mice group treated with PR-HA decreased significantly compared with that of control group. 6. The numbers of CCR3+ cells, CD4+ cells and CD8+ cells in the lungs, and CD3e+/CD69+ in the lungs of the mice group treated with PA-HA decreased significantly compared with those of control group. 7. The mRNA expression of ${\beta}$-actin, TNF-${\alpha}$, IL-4, IL-5, IL-13 in the mice group treated with PR-HA with RT-PCR decreased significantly compared with those of control group. Conclusions : These result suggests that Platycodi Radix Herbal-acupuncture at Joksamni(St36) in C57BL/6mice may be an effictive part to OVA-induced asthma in C57BL/6 mice.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.427-438
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• 2022

Pyroptosis, a form of cell death associated with inflammation, is known to be involved in diabetic nephropathy (DN), and discoid domain receptor 1 (DDR1), an inflammatory regulatory protein, is reported to be associated with diabetes. However, the mechanism underlying DDR1 regulation and pyroptosis in DN remains unknown. We aimed to investigate the effect of DDR1 on renal tubular epithelial cell pyroptosis and the mechanism underlying DN. In this study, we used high glucose (HG)-treated HK-2 cells and rats with a single intraperitoneal injection of streptozotocin as DN models. Subsequently, the expression of pyroptosis-related proteins (cleaved caspase-1, GSDMD-N, Interleukin-1β [IL-1β], and interleukin-18 [IL-18]), DDR1, phosphorylated NF-κB (p-NF-κB), and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes were determined through Western blotting. IL-1β and IL-18 levels were determined using ELISA. The rate of pyroptosis was assessed by propidium iodide (PI) staining. The results revealed upregulated expression of pyroptosisrelated proteins and increased concentration of IL-1β and IL-18, accompanied by DDR1, p-NF-κB, and NLRP3 upregulation in DN rat kidney tissues and HG-treated HK-2 cells. Moreover, DDR1 knockdown in the background of HG treatment resulted in inhibited expression of pyroptosis-related proteins and attenuation of IL-1β and IL-18 production and PI-positive cell frequency via the NF-κB/NLRP3 pathway in HK-2 cells. However, NLRP3 overexpression reversed the effect of DDR1 knockdown on pyroptosis. In conclusion, we demonstrated that DDR1 may be associated with pyroptosis, and DDR1 knockdown inhibited HG-induced renal tubular epithelial cell pyroptosis. The NF-κB/NLRP3 pathway is probably involved in the underlying mechanism of these findings.

• Food Science and Biotechnology
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• v.18 no.1
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• pp.262-266
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• 2009

To evaluate the anticolitic effect of red ginseng (RG, the steamed root of Panax ginseng CA. Meyer, Araliaceae), RG and its representative constituents, ginsenosides Rg3 and Rh2, were orally administered to dextran sulfate sodium (DSS)-induced colitic mice and inflammatory markers investigated. RG and its constituents, ginsenosides Rg3 and Rh2, inhibited colon shortening and myeloperoxidase activity induced by DSS. The ginsenosides Rg3 and Rh2 inhibited mRNA expression of interleukin (IL)-$1{\beta}$ as well as protein levels of IL-$1{\beta}$ and IL-6. These ginsenosides also inhibited the activation of a transcription nuclear factor (NF)-${\kappa}B$. Ginsenoside Rh2 was a more potent inhibitor than ginsenoside Rg3. The anticolitic effects of these ginsenosides were comparable with sulfasalazine.

• Biomedical Science Letters
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• v.24 no.2
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• pp.94-101
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• 2018

Tuberculosis (TB) is infectious disease caused by Mycobacterium tuberculosis (MTB) infection. It is known that not only the property of microorganism but also the genetic susceptibility of infected patients is controlled. Interleukin 2 (IL-2) is a cytokine belonging to type 1 T helper (Th1) activity. In addition, IL-2, when infected with MTB, binds IL-2 receptor and promotes T cell replication and is involved in granuloma formation. The aim of this study was to investigate the genetic polymorphisms of the IL-2 receptor gene in tuberculosis patients and normal individuals. We analyzed 22 SNPs in three genes using the genotype data of 443 tuberculosis cases and 3,228 healthy controls from the Korea Association Resource for their correlation with tuberculosis case. IL2RA, IL2RB, and IL2RG genes were genotyped of 16, 4, and 2 SNPs, respectively. Among three genes, only IL2RA gene polymorphisms showed statistically significant association with tuberculosis case. 6 SNPs with high significance were identified in the IL2RA gene. In addition, the linkage disequilibrium (LD) structure of IL2RA gene was confirmed. SNP imputation of IL2RA gene was performed, it was confirmed that more SNPs were significant between case and control. If we look at the results of IL2RA gene analysis above, we can see that genetic polymorphism in the gene expressing $IL-2R{\alpha}$ will regulate the expression level of $IL-2R{\alpha}$, and the change in the immune system involved in $IL-2R{\alpha}$. In this study, genetic polymorphism that may affect host immunity suggests that susceptibility to tuberculosis may be controlled.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.193-196
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• 2001

IL-18. formerly known as IGIF(interferon -gamma inducing factor), is structurally IL-l related but functionally IL-12 related pro-inflammatory cytokine. The human IL -18(hIL-lS), like IL-$1{\beta}$, is synthesized as a biologically inactive precursor of 24kDa lacking a signal peptide, and then cleaved into an active mature form by cystein protease IL-$1{\beta}$ converting enzyme (ICE: caspase- 1), We tested if the mature hIL -18 can be expressed and secreted into culture medium by transforming the forming gene construct consisting of a mature hIL-18 gene fused to signal peptide of rice amylase lA. Secondly, we were tested if the pro- IL-18 could be processed into a biologically active form by caspase-l like protease in plant. Cell suspension culture was established from the leaf-derived calli of transgenic tobacco plant. Southern and Northern blot analysis indicated the expression of both pro-hIL-18 and mature hIL-18 plant cells. Western blot analysis introduced the protein products of pro- hIL -18 and mhIL -18 were observed in transigenic cell lines. In addition, the molecular size of recombinant pro-hILl-18 and mhIL-18 were estimated to be 24kDa and 18kDa, respectively. ELISA revealed that the amount of pro- hIL -18 was 1.3ug per gram of fresh weight calli. Moreover, the presence of mhIL-18 was detected in the culture medium and it appeared to be 25ug/L.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7857-7861
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• 2014

Natural killer (NK) cells play an important role in anti-tumor immunity. Interleukin (IL)-18 is an immunoregulatory cytokine that induces potent NK cell-dependent anti-tumor responses when administrated with other cytokines. In this study, we explored the effects of combining IL-18 and IL-2 on NK cytotoxicity as well as expression levels of the NK cell receptor NKG2D in vitro. Freshly isolated PBMCs were incubated for 48 h with IL-18 and IL-2, then CD107a expression on $CD3^-CD56^+$ NK cells was determined by three-colour flow cytometry to evaluate the cytotoxicity of NK cells against human erythroleukemia K562 cells and human colon carcinoma HT29 cells. Flow cytometric analysis was also employed to determine NKG2D expression on NK cells. The combined use of IL-18 and IL-2 significantly increased CD107a expression on NK cells compared with using IL-18 or IL-2 alone, suggesting that the combination of these two cytokines exerted synergistic enhancement of NK cytotoxicity. IL-18 also enhanced NKG2D expression on NK cells when administered with IL-2. In addition, blockade of NKG2D signaling with NKG2D-blocking antibody attenuated the up-regulatory effect of combining IL-18 and IL-2 on NK cytolysis. Our data revealed that IL-18 synergized with IL-2 to dramatically enhance the cytolytic activity of human NK cells in a NKG2D-dependent manner. The results appear encouraging for the use of combined IL-18 and IL-2 in tumor immunotherapy.

• Korean Journal of Psychosomatic Medicine
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• v.10 no.2
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• pp.130-141
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• 2002

Objectives : Stress induces alteration of gastrointestinal function in which interleukin (IL) and hypothalamo-pituitary-axis are involved. Depression again is associated with functional gastrointestinal disorders (FGID) and interleukins. The author attempted to look into the role of interleukins in the FGID also the association of depression and stress in this context. Methods : Entered were 20 patients with FGID, diagnosed by Rome IT criteria and 20 healthy controls. Depression was measured by Hamilton Rating Scale for Depression (HAM-D), and stress of the last one year by Schedule of Recent Experience (SRE). Serum levels of IL-$1\beta$, IL-2, IL-6 were measured by Enzyme-linked Immunosorbent Assay and serum cortisol by Fluorescence Polarization Immunoassay. The results were as follows : Results: 1) Serum levels of IL-$1\beta$, IL-2 were significantly lower in the patients with FGID than those in the controls, but level of IL-6 did not differ between two groups. 2) The patient group showed significantly higher level of serum cortisol as well as higher degrees of depression and stress. 3) Positive correlation was noted between depression and serum cortisol, and between depression and IL-2. A trend of negative correlation was seen between depression IL-$1\beta$. Positive correlation was noted between SRE and IL-6 and IL-6 and serum cortisol. Conclusions : It was concluded that FGID might be related to depression and stress. Changes of the interleukins might be involved with elevated cortisol level.

• Transportation Technology and Policy
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• v.5 no.3
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• pp.21-32
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• 2008

• Journal of Periodontal and Implant Science
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• v.38 no.4
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• pp.579-588
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• 2008

Purpose: The purpose of this study was to investigate the association of generalized aggressive periodontitis with IL-6 promoter gene single nucleotide polymorphisms(SNP). Material and Methods: The study population consisted of 52 generalized aggressive periodontitis patients(GAP) and 30 periodontally healthy control subjects, who were systemically healthy non-smokers. Genomic DNA was obtained from buccal swab. The IL-6 promotor SNP at the positions of -597, -572, and -174 were genotyped by amplifying the polymorphic region using polymerase chain reaction(PCR), restriction enzyme digestion and gel electrophoresis. Result: The genotype distributions for G/G, G/A and A/A genotypes of IL-6 -597 were 30.8%, 40.4%, and 28.8% in the GAP group and 53.3%, 40%, and 6.7% in the control group and were statistically different between 2 groups(p<0.05). Allele 2 frequency of IL-6 -597 were significantly higher in the GAP group than the control group(p<0.01). At the position of IL-6 -572, the distribution for C/C, C/G and G/G genotypes were 23.1%, 55.8% and 21.2% in the GAP group and 20%, 33.3%, and 46.7% in the control group. In female subjects, the genotype distribution were significantly different between 2 groups(p<0.01). In male subjects, allele 2 frequency of IL-6-572 was significantly lower in the GAP group than the control group(p<0.05). The genotype distribution of IL-6 -174 in the GAP group were 96.2%, 3.8% for G/G, G/C genotypes whereas only the G/G genotype was detected in the control group. Conclusion: In conclusion, significant associations were found in IL-6 gene promoter(-597, -572) polymorphisms and generalized aggressive periodontitis. Further cohort study will be necessary in larger population.

• Korean Journal of Acupuncture
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• v.27 no.2
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• pp.95-105
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• 2010

Objectives : The purpose of this study is to investigate the effect of Bacillus-fermented Scutellariae Radix acupuncture solution (SB) on interleukin(IL) production in mouse macrophage stimulatedby lipopolysaccaride(LPS). Methods : Productions of interleukins were measured y High-throughput Multiplex Bead based Assay with Bio-plex Suspension Array System based on $xMAP^{(R)}$(multi-analyte profiling beads) technology. To begin with, cell culture supernatant was obtained after treatment with LPS(1 ${\mu}g/mL$) and SB for 24 hour. Then, it was incubated with the antibody-conj${\mu}g$ated beads for 30 minutes. And detection antibody was added and incubated for 30 minutes. After incubating for 30 minutes, Strepavidin-conjugated Phycoerythrin(SAPE) was then added. Incubating for another 30 minutes, the level of SAPE fluorescence was analyzed on Bio-plex Suspension Array System. Results : The results of the experiment are as follows. SB significantly inhibited the LPS-induced production of IL-3($9.15{\pm}0.35$ pg/mL) by $6.92{\pm}0.05,\;7.21{\pm}0.11,\;6.96{\pm}0.33,\;and\;7.45{\pm}0.74$ pg/mL at the concentration of 25, 50, 100, and 200 ${\mu}g/mL$ in mouse macrophage RAW 264.7 cells (p<0.05). SB significantly inhibited the LPS-induced production of IL-5($7.30{\pm}0.48$ pg/mL) by $6.50{\pm}0.29,\;6.30{\pm}0.25,\;6.30{\pm}0.25,\;and\;5.80{\pm}0.25$ pg/mL at the concentration of 25, 50 100, and 200 ${\mg}g/mL$ in RAW 264.7 cells (p<0.05). SB significantly inhibited the LPS-induced productiion of IL-9($17.26{\pm}0.19$ pg/mL) by $15.01{\pm}0.43$ pg/mL at the concentration of 25 ${\mu}g/mL$ in RAW 264.7 cells(p<0.05). SB significantly inhibited the LPS-induced productioh of IL-13($187.80{\pm}2.90$ pg/mL) by $152.80{\pm}4.25,\;172.80{\pm}3.97,\;162.10{\pm}6.67,\;and\;165.30{\pm}11.80$ pg/mL at the concentration fo 25, 50, 100, and 200 ${\mu}g/mL$ in RAW 264.7 cells(p<0.05). SB significantly inhibited the LPS-induced production of IL-17($18.30{\pm}0.95$ pg/mL) by $13.30{\pm}1.25,\;13.80{\pm}1.11,\;13.30{\pm}0.75,\;and\;14.00{\pm}1.08$ pg/mL at the concentration of 25, 50 100, and 200 ${\mu}g/mL$ in RAW 264.7 cells(p<0.05). SB significantly inhibited the LPS-induced production of IL-23($43.90{\pm}0.83$ pg/mL by $39.50{\pm}1.26,\;38.00{\pm}1.78,\;and\;39.60{\pm}2.49$ pg/mL at the concentration of 25, 100, and 200 ${\mu}g/mL$ in RAW 264.7 cells(p<0.05). Conclusions : These results suggest that SB has anti-inflammatory activity related with its inhibition of IL-3, IL-5, IL-13, IL-17, and IL-23 production in macrophages.