• 한국식품영양학회지
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• 제24권2호
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• pp.268-272
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• 2011

전곡류의 섭취와 만성질환의 유병율은 음의 상관관계가 있는 것으로 알려져 있다. 본 연구에서는 선행 연구 결과, 지방축적억제능이 우수한 소재로 선정된 기장의 항염증능 여부를 검증하고자 하였다. 이를 위해 RAW264.7 세포에 기장열수분획($1\;{\mu}g/m\ell$ 및 $10\;{\mu}g/m\ell$)과 lipopolysaccharide(LPS)를 함께 처리한 후, 24시간 배양시켜 염증매개인자들의 분비량 및 mRNA 발현 정도를 측정하였다. 또한 LPS 자극에 대한 첫 번째 신호전달인자로 알려져 있는 interleukin-1 receptor associated kinase-4(IRAK-4)의 단백질 발현 정도를 측정하였다. 본 연구결과, 기장의 열수분획($10\;{\mu}g/m\ell$)은 LPS로 유도된 NO, $PGE_2$, TNF-${\alpha}$, IL-6 및 MCP-1의 생성량 및 mRNA 발현량을 유의적으로 억제하였다(p<0.05). 특히 이들 지표 중 pro-inflammatory cytokine인 TNF-${\alpha}$와 IL-6의 mRNA 발현량이 효과적으로 감소하였다(p<0.01). IRAK-4의 단백질 발현량 또한 유의적으로 감소하여 LPS 자극에 대한 기장열수분획의 항염증능은 toll-like receptor(TLR)를 통한 IRAK-4를 매개로 하는 신호전달체계 조절에 기인하는 것으로 사료된다.

• Journal of Microbiology and Biotechnology
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• 제23권7호
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• pp.1023-1030
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• 2013

Lipoteichoic acid (LTA), uniquely expressed on gram-positive bacteria, is recognized by Toll-like receptor 2 (TLR2) on not only antigen-presenting cells but also activated T cells. Therefore, it is reasonable to assume that LTA is acting on T cells. However, little is known about the effect of LTA on T-cell regulation. In the present study, we investigated the immunomodulatory effects of LTA on $CD4^+$ T cells. Effector $CD4^+$ T cells, induced after co-culture with S. aureus-pulsed dendritic cells, produced high levels of interferon-${\gamma}$, CD25, CD69, and TLRs 2 and 4. When effector $CD4^+$ T cells were treated with LTA, the expressions of the membrane-bound form of transforming growth factor (TGF)-${\beta}$ and forkhead box P3 increased. Coincidently, the proliferation of effector $CD4^+$ T cells was declined after LTA treatment. When TGF-${\beta}$ signaling was blocked by the TGF-${\beta}$ receptor 1 kinase inhibitor, LTA failed to suppress the proliferation of effector $CD4^+$ T cells. Therefore, the present results suggest that LTA suppresses the activity of effector $CD4^+$ T cells by enhancing TGF-${\beta}$ production.

• Asian-Australasian Journal of Animal Sciences
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• 제31권1호
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• pp.138-148
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• 2018

Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0.8 mg ZEN/kg feed. Kidney samples were collected after treatment, and RNA-seq was used to investigate the effects on immune-related genes and gene networks. Results: A total of 186 differentially expressed genes (DEGs) were screened (120 upregulated and 66 downregulated). Gene ontology analysis revealed that the immune response, and cellular and metabolic processes were significantly controlled by these DEGs. The inflammatory stimulation might be an effect of the following enriched Kyoto encyclopedia of genes and genomes pathway analysis found related to immune and disease responses: cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, systemic lupus erythematosus (SLE), tuberculosis, Epstein-Barr virus infection, and chemical carcinogenesis. The effects of DON and ZEN on genome-wide expression were assessed, and it was found that the DEGs associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9, CXCL10, chemokine [C-C motif] ligand 4), proliferation (insulin like growth factor binding protein 4, IgG heavy chain, receptor-type tyrosine-protein phosphatase C, cytochrome P450 1A1, ATP-binding cassette sub-family 8), and other immune response networks (lysozyme, complement component 4 binding protein alpha, oligoadenylate synthetase 2, signaling lymphocytic activation molecule-9, ${\alpha}$-aminoadipic semialdehyde dehydrogenase, Ig lambda chain c region, pyruvate dehydrogenase kinase, isozyme 4, carboxylesterase 1), were suppressed by DON and ZEN. Conclusion: In summary, our results indicate that high concentrations of DON and ZEN suppress the inflammatory response in kidneys, leading to potential effects on immune homeostasis.

• Tuberculosis and Respiratory Diseases
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• 제73권1호
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• pp.1-10
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• 2012

Care of patients with sepsis has improved over the last decade. However, in the recent two years, there was no significant progress in the development of a new drug for critically ill patients. In January 2011, it was announced that the worldwide phase 3 randomized trial of a novel anti-Toll-like receptor-4 compound, eritoran tetrasodium, had failed to demonstrate an improvement in the mortality of patients with severe sepsis. In October 2011, Xigris (drotrecogin alfa, a recombinant activated protein C) was withdrawn from the market following the failure of its worldwide trial that had attempted to demonstrate improved outcome. These announcements were disappointing. The recent failure of 2 promising drugs to further reduce mortality suggests that new approaches are needed. A study was published showing that sepsis can be associated to a state of immunosuppression and loss of immune function in human. However, the timing, incidence, and nature of the immunosuppression remain poorly characterized, especially in humans. This emphasizes the need for a better understanding of sepsis as well as new therapeutic strategies. Many clinical experiences of the extracorporeal membrane oxygenator (ECMO) treatment for adult acute respiratory distress syndrome (ARDS) patients, which is caused by the H1N1 influenza A virus, were reported. The use of ECMO in severe respiratory failure, particularly in the treatment of adult ARDS, is occurring more commonly.

• Journal of Ginseng Research
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• 제46권2호
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• pp.315-319
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• 2022

• Nutrition Research and Practice
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• 제15권6호
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• pp.798-806
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• 2021

BACKGROUND/OBJECTIVES: Obesity is associated with chronic inflammation. The spleen is the largest organ of the lymphatic system and has an important role in immunity. Obesity-induced inflammatory responses are triggered by Toll-like receptor (TLR)-myeloid differentiation primary response 88 (MyD88) pathway signaling. Phenethyl isothiocyanate (PEITC) and 3,3'-diindolylmethane (DIM), major dietary glucosinolates present in cruciferous vegetables, have been reported to produce anti-inflammatory effects on various diseases. However, the effects of PEITC and DIM on the obesity-induced inflammatory response in the spleen are unclear. The purpose of this study was to examine the anti-inflammatory effects of PEITC and DIM on the spleen and their mechanism in high fat/cholesterol diet (HFCD)-fed C57BL/6 mice. MATERIALS/METHODS: We established an animal model of HFCD-induced obesity using C57BL/6 mice. The mice were divided into six groups: normal diet with AIN-93G diet (CON), high fat diet (60% calories from fat) with 1% cholesterol (HFCD), HFCD with PEITC 30 mg/kg/day or 75 mg/kg/day (HFCD+P30, HFCD+P75), and HFCD with DIM 1.5 mg/kg/day or 7.5 mg/kg/day (HFCD+D1.5, HFCD+D7.5). Enzyme-linked immunosorbent assay was used to evaluate pro-inflammatory cytokine secretion. Western blot and quantitative polymerase chain reaction were used to analyze protein and mRNA levels of nuclear factor kappa B (NF-κB) p65, interleukin 6 (IL-6), cyclooxygenase 2 (COX-2), TLR2, TLR4, and MyD88 in spleen tissue. RESULTS: Serum IL-6 levels were significantly higher in the HFCD group than in groups fed a HFCD with PEITC or DIM. Levels of NF-κB p65 protein and TLR2/4, MyD88, NF-κB p65, IL-6, and COX-2 mRNA were significantly higher in the HFCD group than in the CON group and were reduced by the PEITC and DIM supplements. CONCLUSIONS: PEITC- and DIM-supplemented diets improved splenic inflammation by modulating the TLR2/4-MyD88 pathway in HFCD-fed mice. We suggest that dietary glucosinolates may at least partially improve obesity-induced inflammation of the spleen.

• Journal of Ginseng Research
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• 제41권1호
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• pp.43-51
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• 2017

Background: BIOGF1K, a compound K-rich fraction prepared from the root of Panax ginseng, is widely used for cosmetic purposes in Korea. We investigated the functional mechanisms of the anti-inflammatory and antioxidative activities of BIOGF1K by discovering target enzymes through various molecular studies. Methods: We explored the inhibitory mechanisms of BIOGF1K using lipopolysaccharide-mediated inflammatory responses, reporter gene assays involving overexpression of toll-like receptor adaptor molecules, and immunoblotting analysis. We used the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay to measure the antioxidative activity. We cotransfected adaptor molecules, including the myeloid differentiation primary response gene 88 (MyD88) and Toll/interleukin-receptor domain containing adaptor molecule-inducing interferon-${\beta}$ (TRIF), to measure the activation of nuclear factor (NF)-${\kappa}B$ and interferon regulatory factor 3 (IRF3). Results: BIOGF1K suppressed lipopolysaccharide-triggered NO release in macrophages as well as DPPH-induced electron-donating activity. It also blocked lipopolysaccharide-induced mRNA levels of interferon-${\beta}$ and inducible nitric oxide synthase. Moreover, BIOGF1K diminished the translocation and activation of IRF3 and NF-${\kappa}B$ (p50 and p65). This extract inhibited the upregulation of NF-${\kappa}B$-linked luciferase activity provoked by phorbal-12-myristate-13 acetate as well as MyD88, TRIF, and inhibitor of ${\kappa}B$ ($I{\kappa}B{\alpha}$) kinase ($IKK{\beta}$), and IRF3-mediated luciferase activity induced by TRIF and TANK-binding kinase 1 (TBK1). Finally, BIOGF1K downregulated the NF-${\kappa}B$ pathway by blocking $IKK{\beta}$ and the IRF3 pathway by inhibiting TBK1, according to reporter gene assays, immunoblotting analysis, and an AKT/$IKK{\beta}$/TBK1 overexpression strategy. Conclusion: Overall, our data suggest that the suppression of $IKK{\beta}$ and TBK1, which mediate transcriptional regulation of NF-${\kappa}B$ and IRF3, respectively, may contribute to the broad-spectrum inhibitory activity of BIOGF1K.

• 약학회지
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• 제51권1호
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• pp.44-50
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• 2007

Acute septic shock is one of inflammatory diseases mediated by pro-inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$. In this study, we examined the pathological difference and mechanism of lipopolysaccharides isolated from E. coli (E-LPS) or S. abortus (S-LPS) on inducing acute septic shock in ICR mouse. All mice were died by intraperitoneal treatment of S-LPS with 0.75 mg/kg, whereas E-LPS treated with even 3 mg/kg only showed 30% of mice lethal, indicating that S-LPS may be more feasible in triggering a strong septic shock condition. The secretion pattern of TNF-${\alpha}$, a critical pro-inflammatory cytokine in septic shock condition, was also distinct between E-LPS- and S-LPS-treated groups. Thus, S-LPS strikingly increased serum level of TNF-${\alpha}$ (6 ng/ml) at 1 h, while E-LPS just displayed at 2 ng/ml level. However the interaction of S-LPS with LPS receptor toll like receptor (TLR)-4, was not stronger than that of E-LPS, according to experiments with macrophage cell line RAW264.7 cells. Thus, E-LPS rather than S-LPS strongly enhanced the production of TNF-${\alpha}$. Interestingly, S-LPS more strongly up-regulated splenocyte proliferation, compared to E-LPS group, whereas there was no difference between S- or E-LPS treated groups in proliferation of Balb/c- or C57BL/6-originated splenic lymphocytes. Therefore, our data suggest that S-LPS is a more active endotoxin and that the strong septic shock-inducing effect of S-LPS seems due to the enhancement of early TNF-${\alpha}$ production and S-LPS-sensitive lymphocyte proliferation.

• Journal of Veterinary Science
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• 제24권2호
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• pp.20.1-20.13
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• 2023

Background: As Actinobacillus pleuropneumonniae (APP) infection causes considerable losses in the pig industry, there is a growing need to develop effective therapeutic interventions that leverage host immune defense mechanisms to combat these pathogens. Objectives: To demonstrate the role of microRNA (miR)-127 in controlling bacterial infection against APP. Moreover, to investigate a signaling pathway in macrophages that controls the production of anti-microbial peptides. Methods: Firstly, we evaluated the effect of miR-127 on APP-infected pigs by cell count/enzyme-linked immunosorbent assay (ELISA). Then the impact of miR-127 on immune cells was detected. The cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 were evaluated by ELISA. The expression of cytokines (anti-microbial peptides [AMPs]) was assessed using quantitative polymerase chain reaction. The expression level of IL-6, TNF-α and p-P65 were analyzed by western blot. The expression of p65 in the immune cells was investigated by immunofluorescence. Results: miR-127 showed a protective effect on APP-infected macrophage. Moreover, the protective effect might depend on its regulation of macrophage bactericidal activity and the generation of IL-22, IL-17 and AMPs by targeting sphingosine-1-phosphate receptor3 (SIPR3), the element involved in the Toll-like receptor (TLR) cascades. Conclusions: Together, we identify that miR-127 is a regulator of S1PR3 and then regulates TLR/nuclear factor-κB signaling in macrophages with anti-bacterial acticity, and it might be a potential target for treating inflammatory diseases caused by APP.

• 한국자원식물학회지
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• 제35권4호
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• pp.417-427
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• 2022

본 연구에서는 섬괴불나무 열매(LIF), 잎(LIL) 그리고 줄기(LIS) 추출물의 면역증진 활성과 섬괴불나무 열매(LIF) 추출물의 항비만 활성을 평가하였다. 섬괴불나무 열매(LIF), 잎(LIL) 그리고 줄기(LIS) 추출물은 RAW264.7 세포에서 NO, iNOS, COX-2, IL-1𝛽, TNF-𝛼와 같은 면역증진인자의 생성을 증가시켰으며, IL-1𝛽의 발현은 NO생성과 관련된 것으로 보여진다. 면역증진인자은 TLR2/4를 통해 MAPKs중 p38 그리고 JNK를 자극하여 발현이 유도되는 것으로 판단된다. 항비만 실험에서, 섬괴불나무 열매(LIF) 추출물은 AMPK, HSL, ATGL의 발현 증가와 perilipin-1 발현 억제를통해 지질분해를 유도하여 세포 내 지질축적을 억제하는 것으로 나타났으며, 갈색지방세포로의 분화유도와 에너지 대사에 관여하는 인자인 PRDM16, PGC-1𝛼의 발현유도를 통해서도 지질축적을 억제하는 것으로 판단된다. 향후 섬괴불나무 추출물은 건강 보조제 및 기능성 식품으로의 활용이 가능할 것으로 판단되지만, 섬괴물나무 추출물의 어떠한 성분이 면역과 항비만 활성에 영향을 미치는지에 대한 성분분석이 필요하다. 또한, 본 연구는 세포를 이용한 실험으로 정확한 분석을 위해서는 동물모델을 이용한 섬괴불나무 추출물의 면역증진 및 항비만 활성에 관한 추가적인 연구가 진행되어야 할 것이다.