• Title/Summary/Keyword: lipopolysaccaride

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Inhibitors of Nitric Oxide Syntheasis from Phellinus pini in Murine Macrophages (낙엽송층버섯의 Nitric Oxide 생성저해 물질)

  • Jang, Hyun-Jin;Kim, Ahn-Keun;Pyo, Myoung-Yun;Yang, Ki-Sook
    • YAKHAK HOEJI
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    • v.51 no.6
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    • pp.430-434
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    • 2007
  • The anti-inflammatory activity of fruit body of Phellinus pini was investigated by activity-guided fractionation. From the screening of each fraction for the inhibitory activity of NO production in lipopolysaccaride (LPS) activated RAW 264.7 cells, methanol extract and its hexane soluble fraction of Phellinus pini exhibited inhibition of NO production compared with LPS control without toxicity. The hexane soluble fraction showed dose-dependent inhibition of NO production. The active hexane fraction was repeatedly chromatographed over silica gel, ergosta-7,24(28)-dien-3-ol(1) and ergosterol peroxide (2) were isolated and identified. Ergosterol derivatives were inhibited NOS activation, $IC_{50}$ of them were $18.9{\pm}3.9{\mu}M$ (1) and $20.4{\pm}4.5{\mu}M$ (2).

Inhibitory effects of a new iridoids, patridoid I and II on TNF, iNOS and COX-2 expression in cultured murine macrophages

  • Ju, Hye-Kyung;Jung, Hye-Jin;Moon, Tae-Chul;Lee, Eun-Kyung;Baek, Suk-Hwan;An, Ren-Bo;Bae, Ki-Hwan;Son, Kun-Ho;Kim, Hyun-Pyo;Kang, Sam-Sik;Chang, Hyeun-Wook
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.321.2-321.2
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    • 2002
  • Possible role of anti-inflammatory effects of a new iridoids, patridoid I. II and II-A which were isolated from Patrinia saniculaefolia. examined by assessing their effects on tumor necrosis factor $\alpha$ (TN F$\alpha$) and 2 enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccaride (LPS)-stimulated murine macrophage-like cell line RAW 264.7. Among them. patridoid II consistently inhibited the production of TNF$\alpha$ and NO production in a dose dependent manner. But patridoid I and patrioid ll isomer palrioid ll-A. these compounds very weakly inhibited NO producion. Moreover. treatment of macrophage with these compounds, the decrease in NO products was accompanied by a decrease in iNOS protein level as assessed by Western Blot. But these compounds did not affect COX-2 protein expression in LPS-stimulated macrophage. Our results suggest that patridoid ll could become a leading compound for developing a novel of anti-inflammalory drugs.

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Enhancement of Nitric Oxide Production by Corticotropin-releasing Hormone (CRH) in Murine Microglial Cells, BV2 (생쥐 미세아교세포(BV2)에서 Corticotropin-releasing Hormone (CRH)에 의한 Nitric Oxide (NO) 생성의 증가)

  • Yang, Yool-hee;Yang, Young;Cho, Dae-Ho
    • IMMUNE NETWORK
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    • v.4 no.1
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    • pp.60-64
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    • 2004
  • Background: Microglial cells, major immune effector cells in the central nervous system, become activated in neurodegenerative disorders. Activated microglial cells produce proinflammatory mediators such as nitric oxide (NO), tumor necrosis factor-$\alpha$ and interleukin-$1{\beta}$(IL-$1{\beta}$). These proinflammatory mediators have been shown to be significantly increased in the neurodegenerative disorders such as Alzhimer's disease and Pakinson's disease. It was known that one of the neurodegeneration source is stress and it is important to elucidate mechanisms of the stress response for understanding the stress-related disorders and developing improved treatments. Because one of the neuropeptide which plays a main role in regulating the stress response is corticotropin-releasing hormone (CRH), we analyzed the regulation of NO release by CRH in BV2 murine microglial cell as macrophage in the brain. Methods: First, we tested the CRH receptor expression in the mRNA levels by RT-PCR. To test the regulation of NO release by CRH, cells were treated with CRH and then NO release was measured by Griess reagent assay. Results: Our study demonstrated that CRH receptor 1 was expressed in BV2 murine microglial cells and CRH treatment enhanced NO production. Furthermore, additive effects of lipopolysaccaride (LPS) and CRH were confirmed in NO production time dependantly. Conclusion: Taken together, these data indicated that CRH is an important mediator to regulate NO release on microglial cells in the brain during stress.

ERK mediated suppressive effects of Sophora flavescens on Tnf alpha production in BV2 microglial cells (BV2 microglial cells에서 ERK를 통한 고삼의 Tnf alpha 생성 억제효과)

  • Kim, Soo-Cheol;Han, Mi-Young;Park, Hae-Jeong;Jung, Kyung-Hee
    • The Korea Journal of Herbology
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    • v.22 no.2
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    • pp.147-153
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    • 2007
  • Objectives : Sophora flavescens (SF) is widely used in traditional herbal medicine in Korea and is well recognized for its anti-inflammatory effect. However, its effect on Tumornecrosis factor alpha (Tnf) production in BV2 microglial cell is not yet known. Methods : We investigated the effect of SF on the production and expression of Tnf, a well known inflammatory mediator, in lipopolysaccaride (LPS)-activated BV2 microglial cells. Results : The LPS-induced Tnf production was markedly reduced by treatment with SF (50 ${\mu}g/ml$). In reverse transcription polymerase chain reaction (RT-PCR) analysis, SF suppressed the LPS activated expression of Tnf mRNA. In addition, Western blot analysis confirmed that SF suppressed the expression of Tnf. Sophora flavescens also inhibited the LPS-induced phosphylation of extracellular signal-regulated kinases (ERK), which mediate the Tnfproduction signaling pathway whereas LPS-induced phosphylation of p38 mitogen activated protein kinase (p38 MAPK), and c-Jun NH2-terminal kinases (JNK) was not inhibited by SF, which implies that SF suppresses LPS-induced Tnf production via the ERK mediated pathway. Conclusion : Taken together, these findings indicated that SF inhibits LPS-induce Tnf production, and that this inhibitory effect is mediated via the ERK pathway.

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STUDIES ON IMMUNOTOXIC POTENTIAL OF METHAMPHETAMINE (MA) IN Balb/C MICE I. Changes of Lymphoid Organs and Inhibitory Effect of Lymphocyte Proliferation to Mitogen

  • Lim, Chae-Woong;Rim, Byung-Moo;Lee, Ho-Il;Kim, Sang-Ho
    • Toxicological Research
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    • v.11 no.1
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    • pp.9-14
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    • 1995
  • The immune system is partially under the control of the sympathetic and parasymphathetic nervous systems through the regulatory feedback loop. Methamphetamine (MA) is a neurotoxic chemical which affects the neurotransmitter system. The objective of this study was to investigate the immunotoxic effect of MA on the major immune target organ and lymphocyte proliferation to the various mitogens. Female Balb/C mice, 15 to 20 g, were injected subcutaneously with 0, 0.5, or 5 mg MA/kg for 14 consecutive days. In MA treated mice, the body weight gain and relative spleen and thymus weight were decreased in doserelated manner. Histopathologically, there was a paucity of lymphold follicles and germinal centers in the spleen, and thymic cortical atrophy with lymphophagocytosis was prominent. Apoptosis also occurred in germinal centers of spleen and thymic cortex. The threshold and peak of lymphocyte proliferation at various concentration of mitogens showed similar patterns. However, the response to lipopolysaccaride (LPS) and pokeweed mitogen (PWM) in the 5 mg MA/kg treated group showed threshold and peak proliferation at high concentration of mitogens (25${\mu}g$ LPS/ml for MA vs 15${\mu}g$ LPS/ml for control; 60${\mu}g$ PWM/ml for MA vs 45${\mu}g$ PWM/ml for control), which suggest that MA impairs T cell dependent-B cell function. This preliminary study indicated that MA affected the lymphold organs and immune function.

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Genomewide Expression Profile of Forsythia Suspensa on Lipopolysaccaride-induced Activation in Microglial Cells

  • Sohn, Sung-Hwa;Ko, Eun-Jung;Kim, Yang-Seok;Shin, Min-Kyu;Hong, Moo-Chang;Bae, Hyun-Su
    • Molecular & Cellular Toxicology
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    • v.4 no.2
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    • pp.113-123
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    • 2008
  • Microglia, which is the primary immune effector cells in the central nervous system, constitutes the first line of defense against infection and injury in the brain. The goal of this study was to determine the protective (anti-inflammation) mechanisms of forsythia suspense (FS) on LPS-induced activation of BV-2 microglial cells. The effects of FS on gene expression profiles in activated BV-2 microglial cells were evaluated using microarray analysis. BV-2 microglial cells were cultured in a 100mm dish $(1{\times}10^7/dish)$ for 24hr and then pretreated with $1{\mu}g/mL$ FS or left untreated for 30 min. Next, $1{\mu}g/mL$ LPS was added to the samples and the cells were reincubated at $37^{\circ}C$ for 30 min, 1hr, and 3hr. The gene expression profiles of the BV-2 microglial cells varied depending on the FS. The oligonucleotide microarray analysis revealed that MAPK pathway-related genes such as Mitogen activated protein kinase 1 (Mapk1), RAS protein activator like 2 (Rasal2), and G-protein coupled receptor 12 (Gpr12) and nitric oxide biosynthesis-related genes such as nitric oxide synthase 1 (neuronal) adaptor protein (Nos1ap), and dimethylarginine dimethylaminohydrolase 1 (Ddah1) were down regulated in FS-treated BV-2 microglial cells. FS can affect the MAPK pathway and nitric oxide biosynthesis in BV-2 microglial cells.

Protein Kinases as Pharmacological Targets for the Reduction of Interleukin-1 Expression in Lipopolysaccaride-Activated Primary Glial Cell

  • Sun Hu-Nan;Fang Wan;Jin Mei-Hua;Han Ying-Hao;Kim Sun-Uk;Lee Sang-Han;Kim Nam-Soon;Kim Cheol-Hee;Lee Dong-Seok
    • Biomedical Science Letters
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    • v.10 no.4
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    • pp.325-332
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    • 2004
  • Inflammatory factor such as Interleukin-1 play important roles in determining the fate of both acute and chronic neurological disorders. We investigated whether inhibitors of PKC or PTK can serve as pharmacological agents to reduce IL-I production and the mechanisms underlying their pharmacological effects in a mixed population of glia. Inhibitors of PKC such as H7, Go6976 and Ro31-8220 significantly reduced both the mRNA and protein levels of IL-1α and IL-β in lipopolysaccharide-activated primary glial cells. While the PTK inhibitor genistein also significantly reduced the production of these cytokines, it did not affect the expression of their mRNA. Taken together, inhibitors of PKC and PTK could serve as pharmacological agents to reduce IL-1 production. However, the mechanisms underlying their pharmacological effects are different. Our results provide evidence that inhibitors of protein kinases can serve as pharmacological agents to modulate IL-1 production in glial cell, and in turn, alleviate neuronal injury.

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Development of Gel Formulation Containing Alkaloid of Cacao Extract (카카오 추출물의 알칼로이드 성분이 함유된 겔제형의 개발)

  • Kang, Sun -Young
    • Korean Journal of Plant Resources
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    • v.30 no.5
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    • pp.535-541
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    • 2017
  • In this study, methanol (CAMe) and ethanol (CAEt) extract of Theobroma cacao L. were tested to see possibility as natural functional cosmetic agent. Cacao extract and cacao extract loaded gel were evaluated for various properties such as antioxidant, antimicrobial, cell viability, anti-inflammatory. Inhibition of nitric oxide production in lipopolysaccaride (LPS) stimulated raw 264.7cells, at concentration of $0.125{\sim}1{\mu}g/ml$ a dose-dependent manner. Gel formulation (3% extract) were stable for 60day in both extract. In conclusion, gel containing extract of Theobroma cacao L. indicated strong possibility for functional cosmetic ingredient.

Effect of Sea Tangle on Proliferation of Splenocytes from Normal and Diabetic Mice (다시마섭취가 정상과 당뇨쥐의 비장세포 증식에 미치는 영향)

  • 조성희;양경미;배복선;임선아;유리나
    • Journal of Nutrition and Health
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    • v.31 no.6
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    • pp.973-980
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    • 1998
  • To investigate the effect of sea tangle on immune function in normal and diabetic states, 10-week old ICR mice were feed control(C) and sea tangle(5) diets containing 5%(w/w) cellulose and 13.6%(w/w) dry sea tangle for 4 weeks. After 4 weeks, three quarters of mice(CD and SD) were made diabetic by intramuscular injection of streptozotocin(150mg/kg bw). On the 4th day after diabetes was apparent by urinary glucose, one third of diabetic mire(CDG and SDG) were treated with glipizide(20mg/kg bw) and the other third(CDM and SDM) with metformin (500mg/kg bw) orally. Spleen weights of diabetic mice with no hypoglycemic drug treatment appeared to be higher in the sea tangle group(SD) than in control(CD), but were not different when drugs were administered. Data on splenocyte proliferation stimulated by lipopolysaccaride from Salmonella abortus equi(0.l$\mu\textrm{g}$/ml) showed that sea tangle increased mitogen response in normal mice(C group vs S group) and appeared to have the same effect in diabetic mice with or without drug treatment. Splenocyte proliferation induced by concanavalin A(0.1$\mu\textrm{g}$/ml) also showed similar results, although there were not statistically significant. Concentration of interleukin-2(IL-2) released from splenocytes of the S group seemed higher than from the C group, but the IL-2 concentrations were not different among six diabetic groups. Results of fatty acid compositions of splenocyte phospholipids showed that diabetes reduced arachidonic acid/linoleic acid ratios and that sea tangle intake and glipizide treatments increased contents of polyunsaturated fatty acids. It is concluded that dietary sea tangle has a positive effect on splenocyte proliferation under normal condition and could have the same effect under diabetic conditions. IL-2 appears to be one of factors mediating the effect but involvement of membrane fatty arid changes and other unknown factors needs lurker Investigation. (Korean J Nutrition 31(6) : 973-980, 1998)

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Immunotoxicity of Polychlorinated Biphenyls (Aroclor 1254) in Mouse Splenocytes (마우스 비장세포에서의 Polychlorinated Biphenyls(Aroclor 1234)의 면역 독성)

  • 반상자;안광수;김주환;임종준;김수연;기미경;이명숙;조수열;김영훈
    • Toxicological Research
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    • v.19 no.4
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    • pp.277-283
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    • 2003
  • Polychlorinated biphenyls (PCBs) has been widely used as plasticizer, insulator, lubricant, paint and ink. The persistence of PCBs in the environment and their bioaccumulation in living organism make a raise concerns regarding their toxic effects in immune system and subsequent effects on human health. However little has been known about effect of PCB, an endocrine disrupter, on splenocytes. In this study, for identifying the effect on the organs and immune cell of mice by the concentration and time of commercial PCB mixture (Aroclor 1254), each 3 mice were tested at the concentration of 3, 30, 300, 1,000 mg/kg respectively, and their organ's weight were measured in 4, 7, 14 days, respectively. Also according to concentration and time, PCB was evaluated for the effects on splenocyte viability and lipopolysaccaride (LPS) and concanavaline A (Con A)-induced splenocyte proliferation on mice spleen. In liver and lung, there were significantly defferent by concentration and time of PCB (p < 0.0001). In respect of concentration of PCB, no significant effects on mice's liver by Aroclor 1254 concentration below than 300 mg/kg were observed except at the concentration of 1,000 mg/kg doses (p < 0.0001). But there was not significant different change in mice spleen by concentration and time of PCB (p=0.2206) and the mode of weight change of spleen was different to of liver and of lung. Viabilities of splenocytes were decreased following treatment with high concentration of PCB. Also, LPS and Con A-induced cell proliferations were decreased by Aroclor 1254 at 1,000 mg/kg. These data suggest that Aroclor 1254 is the immunotoxic compound that may have an effect on mouse immune system.