• Journal of Chest Surgery
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• v.35 no.6
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• pp.407-419
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• 2002

Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by progressive accumulation of lipids, cells, and extracellular matrix. Matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases(TIMPS) contribute to vascular matrix remodeling in atherosclerosis, and some cytokines may play role in the synthesis or activation of MMPs or TIMPs. Material and Method： We produced experimental atherosclerotic plaques in 9 rabbits by atherogenic hypercholesterol diet for 12 weeks, and 10 other rabbits were used as control group with standard laboratory chow, At that time, 19 rabbits were sacrificed and aorta, coronary arteries and blood specimens were prepared. The expressions of MMP-9, TIMP-2 and interleukin(IL)-18, and the bioactivity of IL-6 were investigated with H&E stain, immunohistochemical stain, immunoblotting(Western blot analysis), and bioassay. Result： Serum cholesterol in the experimental group increased up to 1258$\pm$262 mg/dL(control group： 41$\pm$7 mg/dL). All experimental group showed well-developed atherosclerotic plaques in aorta and coronary artery. The expression of MMP-9 in aorta and coronary artery of the experimental group showed significant increase than that of the control group by immunohistochemistry. Among the experimental group, complicated lesions with intimal rupture or complete luminal occlusion, demonstrated stronger expression of MMP-9. Interestingly, there was no difference in expression of TIMP-2 between the experimental and the control group. These findings were confirmed by Western blot analysis. The bioassay revealed significant up-regulation of serum bioactivity of IL-6 in the experimental group(4819.60$\pm$2021.25 IU/$m\ell$) compared to that of IL-6 in the control group(27.20 $\pm$ 12.19 IU/$m\ell$). IL-18 was expressed in all atherosclerotic plaques, whereas little or no expression was detected in the control group. Conclusion： The increased MMP-9 expression along with the unchanged TIMP-2 expression seem to be contributory factors in extracellular matrix degradation in atherosclerosis. Focal overexpression of MMP-9 may promote plaque destabilization and cause complications of atherosclerotic plaques such as thrombosis with/without acute coronary syndrome. Elevation of IL-6 and IL-18 may be more than just markers of atherosclerosis but actual participants in lesion development. Identification of critical regulatory pathway is important to improve the understanding of the cellular and molecular basis of atherosclerosis and may open the way for novel therapeutic strategies.

• Journal of the Korean Applied Science and Technology
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• v.35 no.2
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• pp.509-518
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• 2018

The purpose of this study was myokine product and role with physical activity and literature review. There is accumulating epidemiological evidence that a physically active life plays an independent role in the protection against type 2 diabetes, cardiovascular disease, colon cancer, dementia and even depression. And myokine has been regarded an important factor of exercise training and brain growth factor for the prevention of Alzheimier's disease. During exercise the release of anti-inflammatory myokine from contracting muscle controled the metabolic response, and IL-4, IL-6, IL-7, IL-10, and IL-15 controled muscle hypertrophy, myogenesis and angiogenenesis. IL-6 promoted the lipid metabolism through AMPK activation. IL-1Ra, IL-10 and sTNF-R inhibited $TNF-{\alpha}$ as the pro-inflammatory cytokine. IL-15 increased the releasing volume from contracting muscle, and promoted the anabolic factor of muscle growth. IL-7 and IL-8 activated the angiogenesis through the more activation of C-X-C receptor signal transmission.

• Journal of dental hygiene science
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• v.23 no.4
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• pp.296-301
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• 2023

Background: Periodontal disease is a major cause of tooth loss in adults and is a representative oral disease commonly suffered by most people around the world. Mainly the proliferation of Gram-negative bacteria and secreted virulence factors cause an inflammatory response and destroy periodontal tissue. Gossypetin, isolated from Hibiscus sabdariffa L, is known to have various pharmacological effects, including antibacterial and anticancer activities. We aimed to confirm the anti-inflammatory effect of gossypetin through interleukin-6 (IL-6) regulation in human gingival fibroblasts (HGFs) stimulated with lipopolysaccharide (LPS) of Porphyromonas gingivalis, a major cause of adult periodontitis. Methods: CCK-8 assay was performed to confirm the concentration-dependent cytotoxicity of gossypetin against HGFs. The secretion level and mRNA expression of IL-6, an inflammation-related cytokine, and the effect of gossypetin on these in HGFs stimulated with P. gingivalis LPS were confirmed by ELISA and qRT-PCR analysis, respectively. Results: Up to a concentration of 100 µM gossypetin with or without P. gingivalis LPS, the survival rate for HGFs was maintained at over 95% and showed no toxicity. ELISA and qRT-PCR analysis results showed that P. gingivalis LPS increased IL-6 secretion and mRNA levels in HGFs compared to the control group. However, this increase in IL-6 was significantly down-regulated by gossypetin treatment in a dose-dependent manner. In particular, 80 µM gossypetin inhibited IL-6 production to the level of the control group. Conclusion: These results indicated that gossypetin attenuated IL-6 production in HGFs stimulated by P. gingivalis LPS, which may ultimately suppress the inflammatory response in periodontal tissue. Therefore, gossypetin may have potential as a natural ingredient for the prevention and treatment of periodontal disease.

• IMMUNE NETWORK
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• v.14 no.3
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• pp.156-163
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• 2014

Interleukin (IL) 17 is produced by T-helper (Th) 17 with a vigorous effect on cells of the immune system playing important roles in pathogenesis of immune-mediated diseases, including autoimmune disorders and cancers. Therefore, the aim of current study was to determine the serum levels of IL-6, IL-17, and transforming growth factor beta (TGF-${\beta}$) in Iranian bladder cancer patients, and to correlate them with disease status. Blood samples were collected from 40 bladder cancer patients and 38 healthy individuals with no history of malignancies or autoimmune disorders. The serum levels of IL-6, IL-17, and TGF-${\beta}$ were measured by the enzyme-linked immunosorbent assay (ELISA). The results showed that the levels of IL-17 (p<0.0001) and TGF-${\beta}$ (p<0.0001) were significantly lower in the patients compared to the controls. No significant differences in the level of serum IL-6 (p=0.16) was observed between the patients and controls. In addition, demographic characteristics between control and patients groups were not significantly different. As most of the cases studied in this investigation were in stage I and II, it is concluded that reduced Th17-related cytokines can be used as indicators for following the course and clinical stages of bladder carcinoma progress and immune response to cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.5
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• pp.238-244
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• 2020

Yangdan-tang (YD) is recorded as a treatment to treat exterior-related fever illness in the Korean medicine. In this study, we examined the anti-inflammatory effects of YD, using YD water extract and lipopolysaccharide (LPS)-induced RAW 264.7 cells. First of all, we measured the amount of nitric oxide (NO) and prostaglandin E2 (PGE2), the products of inflammatory metabolism. Also, we measured enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as cytokines such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1 alpha (IL-1α), and interleukin 1 beta (IL-1β). YD suppressed the production of NO and PGE2 in a dose dependent manner and reduced the amount of protein and the mRNA expression of iNOS and COX-2. Also, YD reduced the mRNA expression of TNF-α, IL-6, IL-1α and IL-1β. In conclusion, YD decreased production of LPS-induced inflammatory factor, which could be a clinical basic subject for inflammatory diseases.

• Journal of Life Science
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• v.25 no.12
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• pp.1377-1383
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• 2015

Scopoletin is a component of several plant such as Erycibe obtusifolia, Aster tataricus, Foeniculum vulgare and Brunfelsia grandiflora. It was reported to have anti-angiogenesis and anti-allergy effects. In this study, the anti-inflammatory effect of scopoletin was investigated in Raw264.7 cells, mouse macrophages. The effects of scopoletin on phagocytosis and nitric oxide (NO) production were investigated in lipopolysaccharide (LPS)-induced inflammatory responses. It was observed that scopoletin exerted inhibitory effects on both phagocytosis and NO production. In addition, scopoletin decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) which were related to NO and prostaglandin E2 (PGE2) production. In particular, the expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The expression levels of IL-1β, IL-6 were remarkably decreased by treatment with scopoletin. Furthermore, the content of TNFα produced by macrophage was decreased in the presence of scopoletin at 8 hr. These results indicate that the anti-inflammatory effect of scopoletin could exert by inhibiting the expression of pro-inflammatory cytokines in Raw264.7 cells stimulated with LPS. The above results suggest scopoletin could be a new remedial agent for anti-inflammation through inhibition of iNOS, COX-2, IL-1β, IL-6 and TNF-α expressions as well as supression of phagocytosis and NO production.

• Journal of Periodontal and Implant Science
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• v.29 no.4
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• pp.979-995
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• 1999

This study was investigated to observe the effect of Treponema denticola cell sonicates(TDC) and Treponema lecithinolyticum cell sonicates(TLC) on cytokine secretion and matix metalloproteinase-2(MMP-2) activation of cultured human gingival fibroblast. Several experiments were performed including $IL-1{\beta}$, IL-6 ELISA for the effect on the $IL-1{\beta}$, IL-6 secretion of human gingival fibroblast. Also gelatinase zymography and gelatin dissolubility test for the activation of MMP-2 secreted by gingival fibroblast. The results were as follows. 1. The effect of TDC and TLC on IL-6 secretion of human gingival fibroblast showed statistically significant increase of IL-6 secretion in the TDC and TLC treated group compared to no treatment group(p<0.05) . 2. The amount of $IL-1{\beta}$ secretion was below the lower limit and there was no difference in the $IL-1{\beta}$ secretion of gingival fibroblast between TDC, TLC treated group and no treatment group. 3. The active form of pro MMP-2 with 72 kDa molecular weight was activated in both TDC and TLC treated group and clear band was appeared at 62kDa site on the zymography. 4. Gelatin dissolubility of MMP-2 secreted by gingival fibroblast was higher in TDC and TLC treated group compared to no treatment group(p<0.05). 5. In the TDC treated group, serine protease of T. denticola affect gelatin dissolubility. But in the TLC treated group gelatin was degraded by only MMP secreted by gingival fibroblast. Regarding to the above results, TDC and TLC have an effect on the IL-6 secretion increase of human gingival fibroblast and appears to activate pro MMP-2 which degrades collagen.

• 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.

• Korean Journal of Microbiology
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• v.45 no.2
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• pp.91-98
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• 2009

Infectious bursal disease (IBD) caused by the infectious bursal disease virus (IBDV) has an important economic impact on the poultry industry worldwide. This study examined the adjuvant effects of a plasmid encoding chicken interleukin-6 (pcDNA-ChIL-6) and levamisole (LMS) on in ovo prime-boost vaccination using a genetic vaccine (pcDNA-VP243) to prime in chicken followed by a killed-vaccine boost. A pcDNA-VP243 was injected into the amniotic sac alone or in combination with a pcDNA-ChIL-6 or LMS at embryonation day 18, followed by an intramuscular injection of killed IBD vaccine at 1 week of age. The chicken were orally challenged with very virulent IBDV (vvIBDV) strain at 3 weeks of age and observed for 10 days. No mortality was observed in the groups that received the pcDNA-VP243 alone and pcDNA-VP243 plus pcDNA-ChIL-6 or LMS compared to 100% mortality in unvaccinated challenge control group. However, as determined by bursal damage (the presence of IBDV RNA, B/B ratio, and lesion score), a pcDNA-VP243 alone group was superior to pcDNA-VP243 plus pcDNA-ChIL-6 or LMS groups in the protection against post-challenge. These findings suggest that in ovo priming with genetic vaccine and boosting with killed vaccine is an effective strategy for protecting chicken against vvIBDV and the addition of pcDNA-ChIL-6 or LMS did not enhance protective immunity.

• BMB Reports
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• v.48 no.5
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• pp.239-240
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• 2015

Dysregulation of cytokine expression causes inflammatory diseases or chronic infection conditions. We have identified that Tat-activating regulatory DNA-binding protein-43 (TDP-43) is involved in cytokine RNA processing in order to promote an optimal immune response. The interaction of TDP-43 with spliceosomal components from the Cajal body leads to the formation of a novel sub-nuclear body called the Interleukin (IL)-6 and IL-10 Splicing Activating Compartment (InSAC). TDP-43 binds to the IL-6 and IL-10 RNAs in a sequence-dependent manner. In cell-based studies, we observed that lipopoly-saccharide (LPS) stimulation induces the formation of the InSAC through TDP-43 ubiquitination, thereby influencing the processing and expression levels of IL-6 RNA. Moreover, TDP-43 knockdown in vivo results in a decrease in IL-6 production and its RNA splicing and stability. Thus, these findings demonstrate that the InSAC is linked to the activation and modulation of the immune response. [BMB Reports 2015; 48(5): 239-240]