• Title/Summary/Keyword: IRF-1,7

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Ginsenoside Rp1, a Ginsenoside Derivative, Blocks Promoter Activation of iNOS and COX-2 Genes by Suppression of an IKKβ-mediated NF-κB Pathway in HEK293 Cells

  • Shen, Ting;Lee, Jae-Hwi;Park, Myung-Hwan;Lee, Yong-Gyu;Rho, Ho-Sik;Kwak, Yi-Seong;Rhee, Man-Hee;Park, Yung-Chul;Cho, Jae-Youl
    • Journal of Ginseng Research
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    • v.35 no.2
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    • pp.200-208
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    • 2011
  • Ginsenoside (G) $Rp_1$ is a ginseng saponin derivative with anti-cancer and anti-inflammatory activities. In this study, we examined the mechanism by which G-$Rp_1$ inhibits inflammatory responses of cells. We did this using a strategy in which DNA constructs containing cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) promoters were transfected into HEK293 cells. G-$Rp_1$ strongly inhibited the promoter activities of COX-2 and iNOS; it also inhibited lipopolysaccharide induced upregulation of COX-2 and iNOS mRNA levels in RAW264.7 cells. In HEK293 cells G-$Rp_1$ did not suppress TANK binding kinase 1-, Toll-interleukin-1 receptor-domain-containing adapter-inducing interferon-${\beta}$ (TRIF)-, TRIF-related adaptor molecule (TRAM)-, or activation of interferon regulatory factor (IRF)-3 and nuclear factor (NF)-${\kappa}$B by the myeloid differentiation primary response gene (MyD88)-induced. However, G-$Rp_1$ strongly suppressed NF-${\kappa}$B activation induced by I${\kappa}$B kinase (IKK)${\beta}$ in HEK293 cells. Consistent with these results, G-$Rp_1$ substantially inhibited IKK${\beta}$-induced phosphorylation of $I{\kappa}B{\alpha}$ and p65. These results suggest that G-$Rp_1$ is a novel anti-inflammatory ginsenoside analog that can be used to treat IKK${\beta}$/NF-${\kappa}$B-mediated inflammatory diseases.

OASL1 Traps Viral RNAs in Stress Granules to Promote Antiviral Responses

  • Kang, Ji-Seon;Hwang, Yune-Sahng;Kim, Lark Kyun;Lee, Sujung;Lee, Wook-Bin;Kim-Ha, Jeongsil;Kim, Young-Joon
    • Molecules and Cells
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    • v.41 no.3
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    • pp.214-223
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    • 2018
  • Oligoadenylate synthetase (OAS) protein family is the major interferon (IFN)-stimulated genes responsible for the activation of RNase L pathway upon viral infection. OAS-like (OASL) is also required for inhibition of viral growth in human cells, but the loss of one of its mouse homolog, OASL1, causes a severe defect in termination of type I interferon production. To further investigate the antiviral activity of OASL1, we examined its subcellular localization and regulatory roles in IFN production in the early and late stages of viral infection. We found OASL1, but not OASL2, formed stress granules trapping viral RNAs and promoted efficient RLR signaling in early stages of infection. Stress granule formation was dependent on RNA binding activity of OASL1. But in the late stages of infection, OASL1 interacted with IRF7 transcripts to inhibit translation resulting in down regulation of IFN production. These results implicate that OASL1 plays context dependent functions in the antiviral response for the clearance and resolution of viral infections.

Effects of Pogonatherum paniceum (Lamk) Hack extract on anti-mitochondrial DNA mediated inflammation by attenuating Tlr9 expression in LPS-induced macrophages

  • Rungthip Thongboontho;Kanoktip Petcharat;Narongsuk Munkong;Chakkraphong Khonthun;Atirada Boondech;Kanokkarn Phromnoi;Arthid Thim-uam
    • Nutrition Research and Practice
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    • v.17 no.5
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    • pp.827-843
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    • 2023
  • BACKGROUND/OBJECTIVES: Mitochondrial DNA leakage leads to inflammatory responses via endosome activation. This study aims to evaluate whether the perennial grass water extract (Pogonatherum panicum) ameliorate mitochondrial DNA (mtDNA) leakage. MATERIALS/METHODS: The major bioactive constituents of P. paniceum (PPW) were investigated by high-performance liquid chromatography, after which their antioxidant activities were assessed. In addition, RAW 264.7 macrophages were stimulated with lipopolysaccharide, resulting in mitochondrial damage. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to examine the gene expression and cytokines. RESULTS: Our results showed that PPW extract-treated activated cells significantly decrease reactive oxygen species and nitric oxide levels by reducing the p2phox and iNOS expression and lowering cytokine-encoding genes, including IL-6, TNF-α, IL-1β, PG-E2 and IFN-γ relative to the lipopolysaccharide (LPS)-activated macrophages. Furthermore, we observed that LPS enhanced the mtDNA leaked into the cytoplasm, increasing the transcription of Tlr9 and signaling both MyD88/Irf7-dependent interferon and MyD88/NF-κb p65-dependent inflammatory cytokine mRNA expression but which was alleviated in the presence of PPW extract. CONCLUSIONS: Our data show that PPW extract has antioxidant and anti-inflammatory activities by facilitating mtDNA leakage and lowering the Tlr9 expression and signaling activation.

Effect of Vigna angularis on Toll-like Receptor Activation and Pro-inflammatory Cytokine Production (적소두 추출물이 톨유사수용체 활성 및 염증유발 사이토카인의 생성에 미치는 영향)

  • Kim, Mi-Hwa;Jeoung, See-Hwa;Lee, Seung-Woong;Kim, Hyun-Kyu;Park, Chan-Sun;Jeon, Byung-Hun;Oh, Hyun-Mee;Rho, Mun-Chual
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.4
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    • pp.511-518
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    • 2012
  • The mechanisms of Toll-like receptor (TLR) signaling have been the focus of extensive studies because TLRs are the target of therapeutic intervention on multiple diseases. In this study, we investigated the inhibitory potential of Vigna angularis (azuki bean) on the TLR signaling. The effect of Vigna angularis extract (JSD) on TLR activation was investigated by assessing NF-${\kappa}B$ and AP-1 inducible secreted embryonic alkaline phosphatase (SEAP) activity. JSD significantly inhibited SEAP activity induced by poly I:C (TLR3 ligand) and poly I (TLR7 ligand) in a dose-dependent manner at concentration below 100 ${\mu}g/ml$ with no sign of cytotoxicity. Pretreatment of JSD markedly suppressed mRNA expressions of pro-inflammatory cytokines and adhesive molecules such as TNF-${\alpha}$, IL-6, RANTES, MCP-1 and ICAM-1 induced by TLR ligands. It also diminished the phosphorylation of $I{\kappa}B$ kinase and $I{\kappa}B$, and followed by $I{\kappa}B$-mediated nuclear translocation of p50, p65, and phosphorylation of p38, JNK, and IRF signaling pathway. In conclusion, our results suggest that Vigna angularis has inhibitory activity on TLR-3 and -7 signaling and it can be further developed as a remedy in curing TLR-related multiple diseases.

Identification of Tumor Suppressor Loci on the Long Arm of Chromosome 5 in Primary Small Cell Lung Cancers (원발성 소세포폐암에서 염색체 5번의 장완에 위치한 종양억제유전자좌의 확인)

  • Cho, Eun-Song;Kim, Ho-Guen;Cho, Chul-Ho;Chang, Joon;Chung, Kyung-Young;Kim, Young-Sam;Park, Jae-Min;Kim, Sung-Kyu;Kim, Se-Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.1
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    • pp.49-59
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    • 2000
  • Backgrounds : Recent cytogenetic studies indicated that long of the long arm of chromosome 5 is a frequent event in small cell lung canær (SCLC), suggesting the presence of a tumor suppressor gene in its place. To map the precise tumor-suppressor loci on the chromosome arm for further positional cloning efforts, we tested 15 primary SCLCs. Methods : The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Nineteen polymorphic microsatellite markers located in the long arm of chromosome 5 were used in the microsatellite analysis. Results : We found that ten (66.7%) of 15 tumors exhibited LOH in at least one of tested microsatellite markers. Two (13%) of 10 tumors exhibiting LOH lost a larger area in chromosome 5q. LOH was observed in five common deleted regions at 5q. Among those areas, LOH between 5q34-qter and 5q35.2-35.3 was most frequent (75%). LOH was also observed in more than 50% of the tumors at four other regions, between 5q14-15 and 5q23-31, 5q31.1, 5q31.3-33.3, and 5q34-35. Three of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Shifted bands occurred in 2.5% (7 of 285) of the loci tested. Conclusion : Our data demonstrated that at least five tumor-suppressor loci exist in the long arm of chromosome 5 and that they may play an important role in small cell lung cancer tumorigenesis.

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Analysis of Causality of the Increase in the Port Congestion due to the COVID-19 Pandemic and BDI(Baltic Dry Index) (COVID-19 팬데믹으로 인한 체선율 증가와 부정기선 운임지수의 인과성 분석)

  • Lee, Choong-Ho;Park, Keun-Sik
    • Journal of Korea Port Economic Association
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    • v.37 no.4
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    • pp.161-173
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    • 2021
  • The shipping industry plummeted and was depressed due to the global economic crisis caused by the bankruptcy of Lehman Brothers in the US in 2008. In 2020, the shipping market also suffered from a collapse in the unstable global economic situation due to the COVID-19 pandemic, but unexpectedly, it changed to an upward trend from the end of 2020, and in 2021, it exceeded the market of the boom period of 2008. According to the Clarksons report published in May 2021, the decrease in cargo volume due to the COVID-19 pandemic in 2020 has returned to the pre-corona level by the end of 2020, and the tramper bulk carrier capacity of 103~104% of the Panamax has been in the ports due to congestion. Earnings across the bulker segments have risen to ten-year highs in recent months. In this study, as factors affecting BDI, the capacity and congestion ratio of Cape and Panamax ships on the supply side, iron ore and coal seaborne tonnge on the demand side and Granger causality test, IRF(Impulse Response Function) and FEVD(Forecast Error Variance Decomposition) were performed using VAR model to analyze the impact on BDI by congestion caused by strengthen quarantine at the port due to the COVID-19 pandemic and the loading and discharging operation delay due to the infection of the stevedore, etc and to predict the shipping market after the pandemic. As a result of the Granger causality test of variables and BDI using time series data from January 2016 to July 2021, causality was found in the Fleet and Congestion variables, and as a result of the Impulse Response Function, Congestion variable was found to have significant at both upper and lower limit of the confidence interval. As a result of the Forecast Error Variance Decomposition, Congestion variable showed an explanatory power upto 25% for the change in BDI. If the congestion in ports decreases after With Corona, it is expected that there is down-risk in the shipping market. The COVID-19 pandemic occurred not from economic factors but from an ecological factor by the pandemic is different from the past economic crisis. It is necessary to analyze from a different point of view than the past economic crisis. This study has meaningful to analyze the causality and explanatory power of Congestion factor by pandemic.