• Title/Summary/Keyword: Nuclear factor-KB

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Evaluation of Goundwater Flow Pattern at the Site of Crystalline Rock using Time Series and Factor Analyses (시계열분석과 요인분석에 의한 결정질 암반의 지하수 유동 평가)

  • Lee, Jeong-Hwan;Jung, Haeryong;Yun, Si-Tae;Kim, Jee-Yeon;Cho, Sung-Il
    • Journal of Soil and Groundwater Environment
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    • v.19 no.4
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    • pp.12-22
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    • 2014
  • This study evaluated the pattern of groundwater fluctuation in cyrstalline rock using time series and factor analyses. From the results, groundwater level for the 18 wells was classified into 4 types reflecting the hydrogeological properties and rainfall event. Type 1 (DB1-5, DB1-6, DB2-2, KB-10, KB-13) was significantly influenced by groundwater flow through water-conducting features, whereas type 2 (DB1-3, DB1-7, KB-1~KB-3, KB-7, KB-11, KB-14, KB-15) was affected by minor fracture network as well as rainfall event. Type 3 (DB1-1, DB1-2) was mainly influenced by surface infiltration of rainfall event. Type 4 (DB1-8, KB-9) was reflected by the irregular variation of groundwater level caused by anisotropy and heterogeneity of crystalline rock.

Anti-Inflammatory Effects of N1-Benzyl-4-Methylbenzene-1,2-Diamine (JSH-21) Analogs on Nitric Oxide Production and Nuclear Factor-kappa B Transcriptional Activity in Lipopolysaccharide-Stimulated Macrophages RAW 264.7

  • Min, Kyung-Rak;Shin, Hyun-Mo;Lee, Jee-Hyun;Kim, Byung-Hak;Chung, Eun-Yong;Jung, Sang-Hun;Kim , Young-Soo
    • Archives of Pharmacal Research
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    • v.27 no.10
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    • pp.1053-1059
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    • 2004
  • $N^1$-Benzyl-4-methylbenzene-1,2-diamine (JSH-21) and its analogs were chemically synthesized and their anti-inflammatory potentials investigated. JSH-21 inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 in a dose-dependent manner, with an $IC_{50}$ value of 9.2 ${\mu}M$, where pyrrolidine dithiocarbamate and parthenolide as positive controls exhibited $IC_{50}$ values of 29.3 and 3.6 ${\mu}M$, respectively. The inhibitory effect of JSH-21 on the NO production was attributable to its down-regulatory action on LPS-inducible NO synthase (iNOS), which was documented by iNOS promoter activity. In the mechanism of the anti-inflammatory action, JSH-21 exhibited inhibitory effects on LPS-induced DNA binding activity and transcriptional activity of nuclear factor-kappa B (NF-$_KB$). Structural analogs of JSH-21 also inhibited both the LPS-induced NO production and NF-$_KB$). transcriptional activity, where diamine substitution at positions 1 and 2 of JSH-21 seems to play an important role in the anti-inflammatory activity.

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Activates Pro-Survival Signaling Pathways, Nuclear Factor-${\kappa}B$ and Extracellular Signal-Regulated Kinase 1/2 in Trophoblast Cell Line, JEG-3

  • Ka Hakhyun
    • Reproductive and Developmental Biology
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    • v.29 no.2
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    • pp.101-108
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    • 2005
  • Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a well-known inducer of apoptotic cell death in many tumor cells. 1RAIL is expressed in human placenta, and cytotrophoblast cells express 1RAIL receptors. However, the role of TRAIL in human placentas and cytotrophoblast cells is not. well understood. In this study a trophoblast cell line, JEG-3, was used as a model system to examine the effect of TRAIL. on key intracellular signaling pathways involved in the control of trophoblastic cell apoptosis and survival JEG-3 cells expressed receptors for 1RAIL, death receptor (DR) 4, DR5, decoy receptor (OcR) 1 and DeR2. Recombinant human TRAIL (rhTRAIL) did not have a cytotoxic effect determined by MIT assay and did not induce apoptotic cell death determined by poly-(ADP-ribose) polymerase cleavage assay. rhTRAIL induced a rapid and transient nuclear translocation of nuclear $factor-{\kappa}B(NF-{\kappa}B)$ determined by immunoblotting using nuclear protein extracts. rhTRAIL rapidly activated extracellular signal-regulated protein kinase (ERK) 1/2 as determined by immnoblotting for phospho-ERK1/2. However, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38MAPK) and Akt (protein kinase B) were not activated by rhTRAIL. The ability of 1RAIL to induce $NF-{\kappa}B$ and ERK1/2 suggests that interaction between TRAIL and its receptors may play an important role in trophoblast cell function during pregnancy.

Mechanism of P-glycoprotein Expression in the SGC7901 Human Gastric Adenocarcinoma Cell Line Induced by Cyclooxygenase-2

  • Gu, Kang-Sheng;Chen, Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2379-2383
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    • 2012
  • Objective: To investigate possible signal pathway involvement in multi-drug resistant P-glycoprotein (P-gp) expression induced by cyclooxygenase-2 (COX-2) in a human gastric adenocarcinoma cell line stimulated with pacliaxel (TAX). Methods: The effects of TAX on SGC7901 cell growth with different doses was assessed by MTT assay, along with the effects of the COX-2 selective inhibitor NS-398 and the nuclear factor-KB (NF-KB) pathway inhibitor pyrrolidine dithiocarbamate (PDTC). Influence on COX-2, NF-KB p65 and P-gp expression was determined by Western blotting. Results: TAX, NS-398 and PDTC all reduced SGC7901 growth, with dosedependence. With increasing dose of TAX, the expression of COX-2, p65 and P-gp showed rising trends, this being reversed by NS-398. PDTC also caused decrease in expression of p65 and P-gp over time. Conclusion: COX-2 may induce the expression of P-gp in SGC7901 cell line via the NF-kappa B pathway with pacliaxel stimulation.

High molecular weight water-soluble chitosan acts as an accelerator of macrophages activation by recombinant interferon ${\gamma}$ via a process involving $_L$-arginine -dependent nitric oxide production

  • Kim, Hyung-Min
    • Advances in Traditional Medicine
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    • v.1 no.1
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    • pp.71-81
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    • 2000
  • High molecular weight water-insoluble chitosan alone has been previously shown to exhibit in vitro stimulatory effect on macrophages nitric oxide (NO) production. However, high molecular weight water-soluble chitosan (WSC) had no effect on NO production by itself. When WSC was used in combination with recombinant $interferon-{\gamma}\;(Rifn-{\gamma})$, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. The optimal effect of WSC on NO synthesis was shown at 24 h after treatment with $rIFN-{\gamma}$. The increased production of NO from $rIFN-{\gamma}$ plus WSC-stimulated RAW 264.7 macrophages was decreased by the treatment with $N^G$ $monomethyl-_L-arginine$. The increase in NO synthesis was reflected, as an increased amounts of inducible NO synthase (iNOS) protein. Synergy between $rIFN-{\gamma}$ and WSC was mainly dependent on WSC-induced nuclear $factor-_KB$ activation. The present results indicate that WSC may provide various activities such as anti-microbial, anti-tumoral, and anti-viral. In addition, since NO has emerged as an important intracellular and intercellular regulatory molecule having functions as diverse as vasodilation, neural communication, cell growth regulation and host defense, it is tempting to hypothesize that this WSC is involved in the local control of the various fundamental processes such as cardiagra, cardiac infarction, impotence etc.

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Astragaloside IV Prevents Obesity-Associated Hypertension by Improving Pro-Inflammatory Reaction and Leptin Resistance

  • Jiang, Ping;Ma, Dufang;Wang, Xue;Wang, Yongcheng;Bi, Yuxin;Yang, Jinlong;Wang, Xuebing;Li, Xiao
    • Molecules and Cells
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    • v.41 no.3
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    • pp.244-255
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    • 2018
  • Low-grade pro-inflammatory state and leptin resistance are important underlying mechanisms that contribute to obesity-associated hypertension. We tested the hypothesis that Astragaloside IV (As IV), known to counteract obesity and hypertension, could prevent obesity-associated hypertension by inhibiting pro-inflammatory reaction and leptin resistance. High-fat diet (HFD) induced obese rats were randomly assigned to three groups: the HFD control group (HF con group), As IV group, and the As IV + ${\alpha}$-bungaratoxin (${\alpha}-BGT$) group (As IV+${\alpha}-BGT$ group). As IV ($20mg{\cdot}Kg^{-1}{\cdot}d^{-1}$) was administrated to rats for 6 weeks via daily oral gavage. Body weight and blood pressure were continuously measured, and NE levels in the plasma and renal cortex was evaluated to reflect the sympathetic activity. The expressions of leptin receptor (LepRb) mRNA, phosphorylated signal transducer and activator of transcription-3 (p-STAT3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), suppressor of cytokine signaling 3 (SOCS3) mRNA, and protein-tyrosine phosphatase 1B (PTP1B) mRNA, pro-opiomelanocortin (POMC) mRNA and neuropeptide Y (NPY) mRNA were measured by Western blot or qRT-PCR to evaluate the hypothalamic leptin sensitivity. Additionally, we measured the protein or mRNA levels of ${\alpha}7nAChR$, inhibitor of nuclear factor ${\kappa}B$ kinase subunit ${\beta}/nuclear$ factor ${\kappa}B$ ($IKK{\beta}/NF-KB$) and pro-inflammatory cytokines ($IL-1{\beta}$ and $TNF-{\alpha}$) in hypothalamus and adipose tissue to reflect the anti-inflammatory effects of As IV through upregulating expression of ${\alpha}7nAChR$. We found that As IV prevented body weight gain and adipose accumulation, and also improved metabolic disorders in HFD rats. Furthermore, As IV decreased BP and HR, as well as NE levels in blood and renal tissue. In the hypothalamus, As IV alleviated leptin resistance as evidenced by the increased p-STAT3, LepRb mRNA and POMC mRNA, and decreased p-PI3K, SOCS3 mRNA, and PTP1B mRNA. The effects of As IV on leptin sensitivity were related in part to the up-regulated ${\alpha}7nAchR$ and suppressed $IKK{\beta}/NF-KB$ signaling and pro-inflammatory cytokines in the hypothalamus and adipose tissue, since co-administration of ${\alpha}7nAChR$ selective antagonist ${\alpha}-BGT$ could weaken the improved effect of As IV on central leptin resistance. Our study suggested that As IV could efficiently prevent obesityassociated hypertension through inhibiting inflammatory reaction and improving leptin resistance; furthermore, these effects of As IV was partly related to the increased ${\alpha}7nAchR$ expression.

3-(4′-hydroxyl-3′, 5′-dimethoxyphenyl) Propionic Acid Suppresses NO Production and Elevates GSH Levels in Murine Macrophages

  • Song, Young-Sun;Choi, Chun-Yeon;Suh, Hongsuk;Song, Yeong-Ok
    • Preventive Nutrition and Food Science
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    • v.9 no.3
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    • pp.270-275
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    • 2004
  • Previous studies have shown that kimchi and kimchi-derived 3-(4'-hydroxyl-3', 5'-dimethoxyphenyl) propionic acid have anti-oxidative and hypolipidemic effects in rats and rabbits. This study was designed to investigate whether chemically synthesized 3-(4'-hydroxyl-3', 5' -dimethoxyphenyl) propionic acid (HDMPPA) may ameliorate oxidative stress through the regulation of nuclear factor KB (NFkB) activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells. Treatment of RAW 264.7 cells with 400 uM of HDMPPA significantly reduced LPS-stimulated nitric oxide (NO) production. Treatments with HDMPPA at 100 uM to 400 uM concentrations significantly elevated glutathione (GSH) level. However, cell viability and thiobarbituric acid-reactive substances (TBARS) concentrations were not affected by the concentrations of HDMPPA used. The specific DNA binding activities of NFKB, a transcription factor which is sensitive to oxidative stress, were not down-regulated by HDMPPA treatments. These results suggest that HDMPPA may have weak anti-oxidative activity against LPS challenge by scavenging NO and stimulating GSH production.

Inhibition of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 by Gamijihwang-tang Via Suppression of Nuclear Factor-B Activation in RAW 264.7 cells

  • Jang Du-Hyun;Kim Ji-Young;Han Eun-Hee;Park Hee-Ok;Kim Dong-Hee;Jeong Hye-Gwang;Yoo Dong-Yeol
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.5
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    • pp.1405-1410
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    • 2005
  • Asthma is recognized today as an inflammatory disease of the lung characterized by acute non-specific airway hypersensitiveness in association with chronic pulmonary inflammation. Gamijihwang-tang(GJT), a fortified prescription of YMJHT, is applied for the treatments of chronic coughing and asthma, and post-delivery coughing and asthma in the gynecology. Also in the clinical practice, GJT is known to be very effective for controlling coughing and asthma as a cold sequoia. In this study, we investigated the effects of GJT on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production, and on the level of inducible nitric oxide synthase (iNOS) and Cyclooxygenase-2 expression in murine macrophage RAW 264.7 cells. We found that GJT inhibited LPS-induced NO and $PGE_2$ production in a dose dependent manner. Furthermore, GJT inhibited the expression of LPS-induced iNOS and COX-2 protein and mRNA expression in RAW 264.7 macrophages. Treatment with GJT of RAW 264.7 cells transfected with a reporter construct indicated a reduced level of LPS-induced nuclear factor-KB (NF-kB) activity and effectively lowered NF-kB binding as measured by transient transfection assay. These results suggest that the main inhibitory mechanism of the GJT may be the reduction of iNOS and COX-2 gene expression through blocking of NF-kB activation.

Inhibition of Interleukin-12 Production in Mouse Macrophages via Decreased Nuclear $Factor-\kappaB$ DNA Binding Activity by Myricetin, a Naturally Occurring Flavonoid

  • Kang Bok Yun;Kim Seung Hyun;Cho Dae Ho;Kim Tae Sung
    • Archives of Pharmacal Research
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    • v.28 no.3
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    • pp.274-279
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    • 2005
  • Pharmacological inhibition of interleukin-12 (IL-12) production may be a therapeutic strategy for preventing the development and progression of disease in experimental models of autoimmunity. In this study, the effects of myricetin, a naturally occurring flavonoid present in fruits, vegetables and medicinal herbs, on the production of IL-12 were investigated in mouse macrophages stimulated with lipopolysaccharide (LPS). Myricetin significantly inhibited the LPS­induced IL-12 production from both primary macrophages and the RAW264.7 monocytic cell-line in a dose-dependent manner. The effect of myricetin on IL-12 gene promoter activation was analyzed by transfecting RAW264.7 cells with IL-12 gene promoter/luciferase constructs. The repressive effect was mapped to a region in the IL-12 gene promoter containing a binding site for NF-${\kappa}B$. Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the NF-${\kappa}B$ site, which significantly decreased upon addition of myricetin, indicating that myricetin inhibited IL-12 production in LPS-activated macrophages via the down­regulation of NF-KB binding activity.