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  1. Aloin Suppresses Lipopolysaccharide-Induced Inflammatory Response and Apoptosis by Inhibiting the Activation of NF-κB

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    Xuan Luo

    2018-02-01

    Full Text Available Numerous herbal-derived natural products are excellent anti-inflammatory agents. Several studies have reported that aloin, the major anthraquinone glycoside obtained from the Aloe species, exhibits anti-inflammatory activity. However, the molecular mechanism of this activity is not well understood. In this report, we found that aloin suppresses lipopolysaccharide-induced pro-inflammatory cytokine secretion and nitric oxide production, and downregulates the expression of tumor necrosis factor alpha (TNF-α, interleukin 6 (IL-6, inducible nitric oxide synthase (iNOS, and cyclooxygenase-2 (COX-2. Aloin inhibits the phosphorylation and acetylation of the NF-κB p65 subunit by suppressing the upstream kinases p38 and Msk1, preventing LPS-induced p65 translocation to the nucleus. We have also shown that aloin inhibits LPS-induced caspase-3 activation and apoptotic cell death. Collectively, these findings suggest that aloin effectively suppresses the inflammatory response, primarily through the inhibition of NF-κB signaling.

  2. Potential role of an antimicrobial peptide, KLK in inhibiting lipopolysaccharide-induced macrophage inflammation.

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    Pornpimon Jantaruk

    Full Text Available Antimicrobial peptides (AMPs are attractive alternatives to antibiotics. Due to their immune modulatory properties, AMPs are at present emerging as promising agents for controlling inflammatory-mediated diseases. In this study, anti-inflammatory potential of an antimicrobial peptide, KLK (KLKLLLLLKLK and its analogs was evaluated in lipopolysaccharide (LPS-induced RAW 264.7 macrophages. The results herein demonstrated that KLK peptide as well as its analogs significantly inhibited the pro-inflammatory mediator nitric oxide (NO, interleukin-1β (IL-1β and tumor necrosis factor-α (TNF-α production in LPS-stimulated RAW 264.7 macrophages in dose-dependent manners, and such inhibitory effects were not due to direct cytotoxicity. When considering inhibition potency, KLK among the test peptides exhibited the most effective activity. The inhibitory activity of KLK peptide also extended to include suppression of LPS-induced production of prostaglandin E2 (PGE2. KLK significantly decreased mRNA and protein expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 as well as mRNA expression of IL-1β and TNF-α. Moreover, KLK inhibited nuclear translocation of nuclear factor-κB (NF-κB p65 and blocked degradation and phosphorylation of inhibitor of κB (IκB. Taken together, these results suggested that the KLK peptide inhibited inflammatory response through the down-regulation of NF-κB mediated activation in macrophages. Since peptide analogs with different amino acid sequences and arrangement were investigated for their anti-inflammatory activities, the residues/structures required for activity were also discussed. Our findings therefore proved anti-inflammatory potential of the KLK peptide and provide direct evidence for therapeutic application of KLK as a novel anti-inflammatory agent.

  3. Saccharomyces boulardii inhibits lipopolysaccharide-induced activation of human dendritic cells and T cell proliferation

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    Thomas, S; Przesdzing, I; Metzke, D; Schmitz, J; Radbruch, A; Baumgart, D C

    2009-01-01

    Saccharomyces boulardii (Sb) is a probiotic yeast preparation that has demonstrated efficacy in inflammatory and infectious disorders of the gastrointestinal tract in controlled clinical trials. Although patients clearly benefit from treatment with Sb, little is known on how Sb unfolds its anti-inflammatory properties in humans. Dendritic cells (DC) balance tolerance and immunity and are involved critically in the control of T cell activation. Thus, they are believed to have a pivotal role in the initiation and perpetuation of chronic inflammatory disorders, not only in the gut. We therefore decided to investigate if Sb modulates DC function. Culture of primary (native, non-monocyte-derived) human myeloid CD1c+CD11c+CD123– DC (mDC) in the presence of Sb culture supernatant (active component molecular weight < 3 kDa, as evaluated by membrane partition chromatography) reduced significantly expression of the co-stimulatory molecules CD40 and CD80 (P < 0·01) and the DC mobilization marker CC-chemokine receptor CCR7 (CD197) (P < 0·001) induced by the prototypical microbial antigen lipopolysaccharide (LPS). Moreover, secretion of key proinflammatory cytokines such as tumour necrosis factor-α and interleukin (IL)-6 were notably reduced, while the secretion of anti-inflammatory IL-10 increased. Finally, Sb supernatant inhibited the proliferation of naive T cells in a mixed lymphocyte reaction with mDC. In summary, our data suggest that Sb may exhibit part of its anti-inflammatory potential through modulation of DC phenotype, function and migration by inhibition of their immune response to bacterial microbial surrogate antigens such as LPS. PMID:19161443

  4. Docosahexaenoic acid ester of phloridzin inhibit lipopolysaccharide-induced inflammation in THP-1 differentiated macrophages.

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    Sekhon-Loodu, Satvir; Ziaullah; Rupasinghe, H P Vasantha

    2015-03-01

    Phloridzin or phlorizin (PZ) is a predominant phenolic compound found in apple and also used in various natural health products. Phloridzin shows poor absorption and cellular uptake due to its hydrophilic nature. The aim was to investigate and compare the effect of docosahexaenoic acid (DHA) ester of PZ (PZ-DHA) and its parent compounds (phloridzin and DHA), phloretin (the aglycone of PZ) and cyclooxygenase inhibitory drugs (diclofenac and nimesulide) on production of pro-inflammatory biomarkers in inflammation-induced macrophages by lipopolysaccharide (LPS)-stimulation. Human THP-1 monocytes were seeded in 24-well plates (5×10(5)/well) and treated with phorbol 12-myristate 13-acetate (PMA, 0.1μg/mL) for 48h to induce macrophage differentiation. After 48h, the differentiated macrophages were washed with Hank's buffer and treated with various concentrations of test compounds for 4h, followed by the LPS-stimulation (18h). Pre-exposure of PZ-DHA ester was more effective in reducing tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) protein levels compared to DHA and nimesulide. However, diclofenac was the most effective in reducing prostaglandin (PGE2) level by depicting a dose-dependent response. However, PZ-DHA ester and DHA were the most effective in inhibiting the activation of nuclear factor-kappa B (NF-κB) among other test compounds. Our results suggest that PZ-DHA ester might possess potential therapeutic activity to treat inflammation related disorders such as type 2 diabetes, asthma, atherosclerosis and inflammatory bowel disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Total glucosides of paeony inhibits lipopolysaccharide-induced proliferation, migration and invasion in androgen insensitive prostate cancer cells.

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    Zhi-Hui Zhang

    Full Text Available Previous studies demonstrated that inflammatory microenvironment promoted prostate cancer progression. This study investigated whether total glucosides of paeony (TGP, the active constituents extracted from the root of Paeonia Lactiflora Pall, suppressed lipopolysaccharide (LPS-stimulated proliferation, migration and invasion in androgen insensitive prostate cancer cells. PC-3 cells were incubated with LPS (2.0 μg/mL in the absence or presence of TGP (312.5 μg /mL. As expected, cells at S phase and nuclear CyclinD1, the markers of cell proliferation, were increased in LPS-stimulated PC-3 cells. Migration activity, as determined by wound-healing assay and transwell migration assay, and invasion activity, as determined by transwell invasion assay, were elevated in LPS-stimulated PC-3 cells. Interestingly, TGP suppressed LPS-stimulated PC-3 cells proliferation. Moreover, TGP inhibited LPS-stimulated migration and invasion of PC-3 cells. Additional experiment showed that TGP inhibited activation of nuclear factor kappa B (NF-κB and mitogen-activated protein kinase (MAPK/p38 in LPS-stimulated PC-3 cells. Correspondingly, TGP attenuated upregulation of interleukin (IL-6 and IL-8 in LPS-stimulated PC-3 cells. In addition, TGP inhibited nuclear translocation of signal transducer and activator of transcription 3 (STAT3 in LPS-stimulated PC-3 cells. These results suggest that TGP inhibits inflammation-associated STAT3 activation and proliferation, migration and invasion in androgen insensitive prostate cancer cells.

  6. Inhibition of lipopolysaccharide-induced inducible nitric oxide synthase and cyclooxygenase-2 expression by xanthanolides isolated from Xanthium strumarium.

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    Yoon, Jeong Hoon; Lim, Hyo Jin; Lee, Hwa Jin; Kim, Hee-Doo; Jeon, Raok; Ryu, Jae-Ha

    2008-03-15

    Three sesquiterpenoids, xanthatin (1), xanthinosin (2), and 4-oxo-bedfordia acid (3) were isolated from Xanthium strumarium as inhibitors of nitric oxide synthesis in activated microglia (IC(50) values: 0.47, 11.2, 136.5 microM, respectively). Compounds 1 and 2 suppressed the expression of iNOS and COX-2 and the activity of NF-kappaB through the inhibition of LPS-induced I-kappaB-alpha degradation in microglia.

  7. Sargachromenol from Sargassum micracanthum Inhibits the Lipopolysaccharide-Induced Production of Inflammatory Mediators in RAW 264.7 Macrophages

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    Eun-Jin Yang

    2013-01-01

    Full Text Available During our ongoing screening program designed to determine the anti-inflammatory potential of natural compounds, we isolated sargachromenol from Sargassum micracanthum. In the present study, we investigated the anti-inflammatory effects of sargachromenol on lipopolysaccharide (LPS-induced inflammation in murine RAW 264.7 macrophage cells and the underlying mechanisms. Sargachromenol significantly inhibited the LPS-induced production of nitric oxide (NO and prostaglandin E2 (PGE2 in a dose-dependent manner. It also significantly inhibited the protein expression of inducible NO synthase (iNOS and cyclooxygenase-2 (COX-2 in a dose-dependent manner in LPS-stimulated macrophage cells. Further analyses showed that sargachromenol decreased the cytoplasmic loss of inhibitor κBα (IκBα protein. These results suggest that sargachromenol may exert its anti-inflammatory effects on LPS-stimulated macrophage cells by inhibiting the activation of the NF-κB signaling pathway. In conclusion, to our knowledge, this is the first study to show that sargachromenol isolated from S. micracanthum has an effective anti-inflammatory activity. Therefore, sargachromenol might be useful for cosmetic, food, or medical applications requiring anti-inflammatory properties.

  8. Haloperidol Suppresses NF-kappaB to Inhibit Lipopolysaccharide-Induced Pro-Inflammatory Response in RAW 264 Cells.

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    Yamamoto, Shunsuke; Ohta, Noriyuki; Matsumoto, Atsuhiro; Horiguchi, Yu; Koide, Moe; Fujino, Yuji

    2016-02-04

    BACKGROUND Haloperidol, a tranquilizing agent, is administered both to treat symptoms of psychotic disorders and to sedate agitated and delirious patients. Notably, haloperidol has been suggested to inhibit the immune response through unknown mechanisms. We hypothesized that the sedative modulates the immune response via NF-κB. MATERIAL AND METHODS Using flow cytometry, we analyzed the effects of haloperidol on expression CD80 and CD86 in RAW 264 cells and in primary macrophages derived from bone marrow. Secretion of interleukin (IL)-1β, IL-6, and IL-12 p40 was measured by enzyme-linked immunosorbent assay. In addition, NF-κB activation was evaluated using a reporter assay based on secretory embryonic alkaline phosphatase. Finally, synthetic antagonists were used to identify the dopamine receptor that mediates the effects of haloperidol. RESULTS Haloperidol inhibited NF-κB activation, and thereby suppressed expression of CD80, as well as secretion of IL-1β, IL-6, and IL-12 p40. CD80 and IL-6 levels were similarly attenuated by a D2-like receptor antagonist, but not by a D1-like receptor antagonist. CONCLUSIONS The data strongly suggest that haloperidol inhibits the immune response by suppressing NF-kB signaling via the dopamine D2 receptor.

  9. COL-3, a chemically modified tetracycline, inhibits lipopolysaccharide-induced microglia activation and cytokine expression in the brain.

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    Rawan Abdulhameed Edan

    Full Text Available Microglia activation results in release of proinflammatory molecules including cytokines, which contribute to neuronal damage in the central nervous system (CNS if not controlled. Tetracycline antibiotics such as minocycline inhibit microglial activation and cytokine expression during CNS inflammation. In the present study we found that administration of chemically modified tetracycline-3 (COL-3, inhibits lipopolysaccharide (LPS-induced microglial and p38 MAPK activation, as well as the increase in TNF-α, but not IL-1β expression, in the brains of BALB/c mice. COL-3 has been described to have no antibacterial activity. We observed that COL-3 had no activity against a Gram-negative bacteria, Escherichia coli; however surprisingly, COL-3 had antibacterial activity against a Gram-positive bacteria Staphylococcus aureus, with a minimum inhibitory concentration of 1 mg/ml. Our data show that COL-3 has some antibacterial activity against S. aureus, inhibits LPS-induced neuroinflammation, and displays potential as a therapeutic agent for treatment of conditions involving CNS inflammation.

  10. The alpha2-adrenoreceptor agonist dexmedetomidine protects against lipopolysaccharide-induced apoptosis via inhibition of gap junctions in lung fibroblasts.

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    Zhang, Yuan; Tan, Xiaoming; Xue, Lianfang

    2018-01-01

    The α2-adrenoceptor inducer dexmedetomidine protects against acute lung injury (ALI), but the mechanism of this effect is largely unknown. The present study investigated the effect of dexmedetomidine on apoptosis induced by lipopolysaccharide (LPS) and the relationship between this effect and gap junction intercellular communication in human lung fibroblast cell line. Flow cytometry was used to detect apoptosis induced by LPS. Parachute dye coupling assay was used to measure gap junction function, and western blot analysis was used to determine the expression levels of connexin43 (Cx43). The results revealed that exposure of human lung fibroblast cell line to LPS for 24 h increased the apoptosis, and pretreatment of dexmedetomidine and 18α-GA significantly reduced LPS-induced apoptosis. Dexmedetomidine exposure for 1 h inhibited gap junction function mainly via a decrease in Cx43 protein levels in human lung fibroblast cell line. These results demonstrated that the inhibition of gap junction intercellular communication by dexmedetomidine affected the LPS-induced apoptosis through inhibition of gap junction function by reducing Cx43 protein levels. The present study provides evidence of a novel mechanism underlying the effects of analgesics in counteracting ALI. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Dopamine inhibits lipopolysaccharide-induced nitric oxide production through the formation of dopamine quinone in murine microglia BV-2 cells

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    Yasuhiro Yoshioka

    2016-02-01

    Full Text Available Dopamine (DA has been suggested to modulate functions of glial cells including microglial cells. To reveal the regulatory role of DA in microglial function, in the present study, we investigated the effect of DA on lipopolysaccharide (LPS-induced nitric oxide (NO production in murine microglial cell line BV-2. Pretreatment with DA for 24 h concentration-dependently attenuated LPS-induced NO production in BV-2 cells. The inhibitory effect of DA on LPS-induced NO production was not inhibited by SCH-23390 and sulpiride, D1-like and D2-like DA receptor antagonists, respectively. In addition, pretreatment with (−-(6aR,12bR-4,6,6a,7,8,12b-Hexahydro-7-methylindolo[4,3-a]phenanthridin (CY 208–243 and bromocriptine, D1-like and D2-like DA receptor agonists, respectively, did not affect the LPS-induced NO production. N-Acetylcysteine, which inhibits DA oxidation, completely inhibited the effect of DA. Tyrosinase, which catalyzes the oxidation of DA to DA quionone (DAQ, accelerated the inhibitory effect of DA on LPS-induced NO production. These results suggest that DA attenuates LPS-induced NO production through the formation of DAQ in BV-2 cells.

  12. Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-κB activation

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    Tanaka, S; Nishiumi, S; Nishida, M; Mizushina, Y; Kobayashi, K; Masuda, A; Fujita, T; Morita, Y; Mizuno, S; Kutsumi, H; Azuma, T; Yoshida, M

    2010-01-01

    Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-α-evoked translocation of nuclear factor (NF)-κB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-κB and production of TNF-α in mouse macrophage RAW264·7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-α level and inhibited the LPS-evoked nuclear translocation of NF-κB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS. PMID:20030669

  13. Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-kappaB activation.

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    Tanaka, S; Nishiumi, S; Nishida, M; Mizushina, Y; Kobayashi, K; Masuda, A; Fujita, T; Morita, Y; Mizuno, S; Kutsumi, H; Azuma, T; Yoshida, M

    2010-05-01

    Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-alpha-evoked translocation of nuclear factor (NF)-kappaB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-kappaB and production of TNF-alpha in mouse macrophage RAW264.7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-alpha level and inhibited the LPS-evoked nuclear translocation of NF-kappaB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS.

  14. Baicalin Inhibits Lipopolysaccharide-Induced Inflammation Through Signaling NF-κB Pathway in HBE16 Airway Epithelial Cells.

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    Dong, Shou-jin; Zhong, Yun-qing; Lu, Wen-ting; Li, Guan-hong; Jiang, Hong-li; Mao, Bing

    2015-08-01

    Baicalin, a flavonoid monomer derived from Scutellaria baicalensis called Huangqin in mandarin, is the main active ingredient contributing to S. baicalensis' efficacy. It is known in China that baicalin has potential therapeutic effects on inflammatory diseases. However, its anti-inflammatory mechanism has still not been fully interpreted. We aim to investigate the anti-inflammatory effect of baicalin on lipopolysaccharide (LPS)-induced inflammation in HBE16 airway epithelial cells and also to explore the underlying signaling mechanisms. The anti-inflammatory action of baicalin was evaluated in human airway epithelial cells HBE16 treated with LPS. Airway epithelial cells HBE16 were pretreated with a range of concentrations of baicalin for 30 min and then stimulated with 10 μg/ml LPS. The secretions of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in cell culture supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expressions of IL-6, IL-8, and TNF-α were tested by quantitative real-time polymerase chain reaction (real-time RT-PCR). Furthermore, Western blotting was used to determine whether the signaling pathway NF-κB was involved in the anti-inflammatory action of baicalin. The inflammatory cell model was successfully built with 10 μg/ml LPS for 24 h in our in vitro experiments. Both the secretions and the mRNA expressions of IL-6, IL-8, and TNF-α were significantly inhibited by baicalin. Moreover, the expression levels of phospho-IKKα/β and phospho-NF-κB p65 were downregulated, and the phospho-IκB-α level was upregulated by baicalin. These findings suggest that the anti-inflammatory properties of baicalin may be resulted from the inhibition of IL-6, IL-8, and TNF-α expression via preventing signaling NF-κB pathway in HBE16 airway epithelial cells. In addition, this study provides evidence to understand the therapeutic effects of baicalin on inflammatory diseases in

  15. Puerarin exerts antipyretic effect on lipopolysaccharide-induced fever in rats involving inhibition of pyrogen production from macrophages.

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    Yao, Xiu-Juan; Yin, Ji-Ai; Xia, Yu-Feng; Wei, Zhi-Feng; Luo, Yu-Bin; Liu, Mei; Feleder, Carlos; Dai, Yue

    2012-05-07

    Puerarin is the most abundant isoflavonoid in Radix Puerariae (Gegen), which has been prescribed as a medicinal herb for treating fever in China for a long history. The present study aimed at evaluating the antipyretic effect of puerarin and revealing the related mechanisms. Lipopolysaccharide (LPS)-induced fever in rats was used to assess the antipyretic effect of puerarin. After an intraperitoneal injection of LPS (100μg/kg), body temperature was tested every 30min up to 8h. Different doses of puerarin (25, 50, 100mg/kg) were intraperitoneally administered 30min before LPS injection. In vitro, LPS-stimulated RAW 264.7 cells were treated with various concentrations of puerarin (25-200μM). The pyrogenic mediators, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E(2) (PGE(2)) and nitric oxide (NO), were examined on both transcription and expression levels. Furthermore, the influences of the activation of nuclear factor-kappa B (NF-κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs) by puerarin were assayed by western blot. The intraperitoneal administration of puerarin at test doses clearly demonstrated apparent antipyretic effect through the declines in body temperature elevated by LPS in rats. The in vitro data showed that puerarin inhibited the production of IL-1β, TNF-α, IL-6, PGE(2) and NO; moreover, the RT-PCR analysis and the western blot analysis indicated that puerarin regulated the transcriptional level via suppression of NF-κB activation and blockade of MAPK signal pathway. In summary, the antipyretic property of puerarin might result, at least in part, from an inhibition of endogenous pyrogen production and expression. Taken in this sense, our findings provide an explanation for puerarin acting as an important constituent in Gegen, thus, provide scientific basis for the wide use of Radix Puerariae in China as a traditional antipyretic. Copyright © 2012 Elsevier Ireland

  16. Vildagliptin ameliorates pulmonary fibrosis in lipopolysaccharide-induced lung injury by inhibiting endothelial-to-mesenchymal transition.

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    Suzuki, Toshio; Tada, Yuji; Gladson, Santhi; Nishimura, Rintaro; Shimomura, Iwao; Karasawa, Satoshi; Tatsumi, Koichiro; West, James

    2017-10-16

    cells or GLP-1. Inhibiting DPP-4 signaling by vildagliptin could ameliorate pulmonary fibrosis by downregulating EndMT in systemic LPS-induced lung injury.

  17. Inhibition of c-Jun N-terminal Kinase Signaling Pathway Alleviates Lipopolysaccharide-induced Acute Respiratory Distress Syndrome in Rats

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    Jian-Bo Lai

    2016-01-01

    Conclusions: Inhibiting JNK alleviated LPS-induced acute lung inflammation and had no effects on pulmonary edema and fibrosis. JNK inhibitor might be a potential therapeutic medication in ARDS, in the context of reducing lung inflammatory.

  18. Arctigenin inhibits lipopolysaccharide-induced iNOS expression in RAW264.7 cells through suppressing JAK-STAT signal pathway.

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    Kou, Xianjuan; Qi, Shimei; Dai, Wuxing; Luo, Lan; Yin, Zhimin

    2011-08-01

    Arctigenin has been demonstrated to have an anti-inflammatory function, but the precise mechanisms of its action remain to be fully defined. In the present study, we determined the effects of arctigenin on lipopolysaccharide (LPS)-induced production of proinflammatory mediators and the underlying mechanisms involved in RAW264.7 cells. Our results indicated that arctigenin exerted its anti-inflammatory effect by inhibiting ROS-dependent STAT signaling through its antioxidant activity. Arctigenin also significantly reduced the phosphorylation of STAT1 and STAT 3 as well as JAK2 in LPS-stimulated RAW264.7 cells. The inhibitions of STAT1 and STAT 3 by arctigenin prevented their translocation to the nucleus and consequently inhibited expression of iNOS, thereby suppressing the expression of inflammation-associated genes, such as IL-1β, IL-6 and MCP-1, whose promoters contain STAT-binding elements. However, COX-2 expression was slightly inhibited at higher drug concentrations (50 μM). Our data demonstrate that arctigenin inhibits iNOS expression via suppressing JAK-STAT signaling pathway in macrophages. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  19. Resolvin D1 Protects Lipopolysaccharide-induced Acute Kidney Injury by Down-regulating Nuclear Factor-kappa B Signal and Inhibiting Apoptosis

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    Yu-Liang Zhao

    2016-01-01

    Conclusion: In LPS-induced AKI, RvD1 could decrease TNF-α level, ameliorate kidney pathological injury, protect kidney function, and improve animal survival by down-regulating NF-κB inflammatory signal as well as inhibiting renal cell apoptosis.

  20. Gardenia jasminoides extracts and gallic acid inhibit lipopolysaccharide-induced inflammation by suppression of JNK2/1 signaling pathways in BV-2 cells

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    Wen-Hung Lin

    2015-06-01

    Conclusion:Taken together, these results indicate that the protective mechanism of the GJ extract involves an antioxidant effect and inhibition of JNK2/1 MAP kinase and COX-2 expressions in LPS-induced inflammation of BV-2 cells.

  1. Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites

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    Bonin, Camila P., E-mail: mila_bonin@yahoo.com.br [Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900 (Brazil); Baccarin, Raquel Y.A., E-mail: baccarin@usp.br [Department of Clinics, School of Veterinary Medicine, University of São Paulo, São Paulo 05508-900 (Brazil); Nostell, Katarina, E-mail: katarina.nostell@slu.se [Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, 750 07 Uppsala (Sweden); Nahum, Laila A., E-mail: laila@nahum.com.br [Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte 30190-002 (Brazil); Faculdade Infórium de Tecnologia, Belo Horizonte 30130-180 (Brazil); Fossum, Caroline, E-mail: caroline.fossum@bvf.slu.se [Department of Biomedicine and Veterinary Public Health, Section for Immunology, Swedish University of Agricultural Sciences, BMC, Box 588, SE 751 23 Uppsala (Sweden); Camargo, Maristela M. de, E-mail: mmcamar@usp.br [Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900 (Brazil)

    2013-03-08

    Highlights: ► Chimpanzees, horses and humans have regions of similarity on TLR4 and MD2 promoters. ► Rodents have few regions of similarity on TLR4 promoter when compared to primates. ► Conserved NFkB binding sites were found in the promoters of TLR4 and MD2. ► LPS-induced inhibition of TLR4 transcription is reversed by dexamethasone. ► LPS-induced transcription of MD2 is inhibited by dexamethasone. -- Abstract: Engagement of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) is a master trigger of the deleterious effects of septic shock. Horses and humans are considered the most sensitive species to septic shock, but the mechanisms explaining these phenomena remain elusive. Analysis of tlr4 promoters revealed high similarity among LPS-sensitive species (human, chimpanzee, and horse) and low similarity with LPS-resistant species (mouse and rat). Four conserved nuclear factor kappa B (NFκB) binding sites were found in the tlr4 promoter and two in the md2 promoter sequences that are likely to be targets for dexamethasone regulation. In vitro treatment of equine peripheral blood mononuclear cells (eqPBMC) with LPS decreased transcripts of tlr4 and increased transcription of md2 (myeloid differentiation factor 2) and cd14 (cluster of differentiation 14). Treatment with dexamethasone rescued transcription of tlr4 after LPS inhibition. LPS-induced transcription of md2 was inhibited in the presence of dexamethasone. Dexamethasone alone did not affect transcription of tlr4 and md2.

  2. Yi Qi Qing Re Gao-containing serum inhibits lipopolysaccharide-induced rat mesangial cell proliferation by suppressing the Wnt pathway and TGF-β1 expression.

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    Yang, Liping; Sun, Xueyan; Zhan, Yongli; Liu, Huijie; Wen, Yumin; Mao, Huimin; Dong, X I; Li, Ping

    2016-04-01

    The aim of the present study was to investigate the effect of Yi Qi Qing Re Gao-containing serum (YQ-S) on rat mesangial cell (MC) proliferation and to investigate the underlying mechanism. MCs were divided into the control, lipopolysaccharide (LPS)-stimulated, YQ-S and fosinopril-containing serum (For-S) groups, and cultured for 48 h. An MTT assay was used to evaluate the proliferation of MCs. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were conducted to detect the expression levels of Wnt4, β-catenin and transforming growth factor (TGF)-β1 in MCs. The results indicated that YQ-S inhibited LPS-induced MC proliferation. The Wnt4 and TGF-β1 mRNA expression levels were reduced in the YQ-S group (P<0.01 or P<0.05). Furthermore, the Wnt4, β-catenin and TGF-β1 protein expression levels were suppressed in the YQ-S group (P<0.01 or P<0.05). Therefore, YQ-S appears to inhibit MC proliferation, and its mechanism may involve the inhibition of the Wnt signaling pathway and downregulation of TGF-β1 expression.

  3. Oleamide suppresses lipopolysaccharide-induced expression of iNOS and COX-2 through inhibition of NF-kappaB activation in BV2 murine microglial cells.

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    Oh, Young Taek; Lee, Jung Yeon; Lee, Jinhwa; Lee, Ju Hie; Kim, Ja-Eun; Ha, Joohun; Kang, Insug

    2010-05-03

    Oleamide (cis-9-octadecenamide) is an endogenous sleep-inducing fatty acid amide that accumulates in the cerebrospinal fluid of the sleep-deprived animals. Microglia are the major immune cells involved in neuroinflammation causing brain damage during infection, ischemia, and neurodegenerative disease. In this study, we examined the effects of oleamide on LPS-induced production of proinflammatory mediators and the mechanisms involved in BV2 microglia. Oleamide inhibited LPS-induced production of NO and prostaglandin E2 as well as expression of iNOS and COX-2. We showed that oleamide blocked LPS-induced NF-kappaB activation and phosphorylation of inhibitor kappaB kinase (IKK). We also showed that oleamide inhibited LPS-induced phosphorylation of Akt, p38 MAPK, and ERK, activation of PI 3-kinase, and accumulation of reactive oxygen species (ROS). Finally, we showed that a specific antagonist of the CB2 receptor, AM630, blocked the inhibitory effects of oleamide on LPS-induced production of proinflammatory mediators and activation of NF-kappaB. Taken together, our results suggest that oleamide shows an anti-inflammatory effect through inhibition of NF-kappaB activation in LPS-stimulated BV2 microglia. 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Peroxisome proliferator-activated receptor δ inhibits Porphyromonas gingivalis lipopolysaccharide-induced activation of matrix metalloproteinase-2 by downregulating NADPH oxidase 4 in human gingival fibroblasts.

    Science.gov (United States)

    Yoo, T; Ham, S A; Hwang, J S; Lee, W J; Paek, K S; Oh, J W; Kim, J H; Do, J T; Han, C W; Kim, J H; Seo, H G

    2016-10-01

    We investigated the roles of peroxisome proliferator-activated receptor δ (PPARδ) in Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS)-induced activation of matrix metalloproteinase 2 (MMP-2). In human gingival fibroblasts (HGFs), activation of PPARδ by GW501516, a specific ligand of PPARδ, inhibited Pg-LPS-induced activation of MMP-2 and generation of reactive oxygen species (ROS), which was associated with reduced expression of NADPH oxidase 4 (Nox4). These effects were significantly smaller in the presence of small interfering RNA targeting PPARδ or the specific PPARδ inhibitor GSK0660, indicating that PPARδ is involved in these events. In addition, modulation of Nox4 expression by small interfering RNA influenced the effect of PPARδ on MMP-2 activity, suggesting a mechanism in which Nox4-derived ROS modulates MMP-2 activity. Furthermore, c-Jun N-terminal kinase and p38, but not extracellular signal-regulated kinase, mediated PPARδ-dependent inhibition of MMP-2 activity in HGFs treated with Pg-LPS. Concomitantly, PPARδ-mediated inhibition of MMP-2 activity was associated with the restoration of types I and III collagen to levels approaching those in HGFs not treated with Pg-LPS. These results indicate that PPARδ-mediated downregulation of Nox4 modulates cellular redox status, which in turn plays a critical role in extracellular matrix homeostasis through ROS-dependent regulation of MMP-2 activity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Sterols from Hericium erinaceum and their inhibition of TNF-α and NO production in lipopolysaccharide-induced RAW 264.7 cells.

    Science.gov (United States)

    Li, Wei; Zhou, Wei; Cha, Ji Yun; Kwon, Se Uk; Baek, Kwang-Hyun; Shim, Sang Hee; Lee, Young Mi; Kim, Young Ho

    2015-07-01

    Erinarols G-J and 10 known ergostane-type sterols were isolated from a methanol extract of the dried fruiting bodies of Hericium erinaceum. Their chemical structures were elucidated using extensive spectroscopic analyses including 1D and 2D NMR experiments and HR-ESI-MS analysis, as well as through comparison with previously reported data. Anti-inflammatory effects of the isolated compounds were evaluated in terms of inhibition of tumor necrosis factor α (TNF-α) and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cells. The results showed that erinarols H and J, as well as 2 of the ergostane-type sterols exhibited inhibitory activity against TNF-α secretion, with inhibition values ranging from 33.7% to 43.3% at 10 μM. Erinarols J and three ergostane-type sterols exhibited significant inhibitory effects against NO production, with inhibition values ranging from 38.4% to 71.5% at 10 μM. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Extract of corn silk (stigma of Zea mays) inhibits the tumour necrosis factor-alpha- and bacterial lipopolysaccharide-induced cell adhesion and ICAM-1 expression.

    Science.gov (United States)

    Habtemariam, S

    1998-05-01

    Treatment of human endothelial cells with cytokines such as tumour necrosis factor-alpha (TNF) or E. coli lipopolysaccharide (LPS) induces the expression of several adhesion molecules and enhances leukocyte adhesion to endothelial cell surface. Interfering with this leukocyte adhesion or adhesion molecules upregulation is an important therapeutic target for the treatment of bacterial sepsis and various inflammatory diseases. In the course of screening marketed European anti-inflammatory herbal drugs for TNF antagonistic activity, a crude ethanolic extract of corn silk (stigma of Zea mays) exhibited significant activity. The extract at concentrations of 9-250 micrograms/ml effectively inhibited the TNF- and LPS-induced adhesiveness of EAhy 926 endothelial cells to monocytic U937 cells. Similar concentration ranges of corn silk extract did also block the TNF and LPS but not the phorbol 12-myristate 13-acetate-induced ICAM-1 expression on EAhy 926 endothelial cell surface. The extract did not alter the production of TNF by LPS-activated macrophages and failed to inhibit the cytotoxic activity of TNF. It is concluded that corn silk possesses important therapeutic potential for TNF- and LPS-mediated leukocyte adhesion and trafficking.

  7. Curcumin Protects against 1-Methyl-4-phenylpyridinium Ion- and Lipopolysaccharide-Induced Cytotoxicities in the Mouse Mesencephalic Astrocyte via Inhibiting the Cytochrome P450 2E1

    Directory of Open Access Journals (Sweden)

    Hai-Yan Gui

    2013-01-01

    Full Text Available Curcumin is extracted from the rhizomes of the ginger family plant Curcuma longa L., which has a good protection for liver, kidney, and immune system. However, there is little information about its contribution in protection of astrocytes recently. The present study was undertaken to elucidate the protective effect of curcumin, an herbal antioxidant, on 1-methyl-4-phenylpyridinium ion- (MPP+- and lipopolysaccharide- (LPS- induced cytotoxicities, as well as the underlying mechanisms by using primary mouse mesencephalic astrocytes. The results showed that curcumin protected the mesencephalic astrocytes from MPP+- and LPS-induced toxicities along with reducing reactive oxygen species (P<0.05 and maleic dialdehyde (P<0.05 sufficiently. Moreover, curcumin significantly inhibited the cytochrome P450 2E1 (CYP2E1 expression (P<0.01 at mRNA level, P<0.05 at protein level and its activity (P<0.05 sufficiently induced by MPP+ and LPS in the mouse mesencephalic astrocytes. And curcumin as well as diallyl sulphide, a CYP2E1 positive inhibitor, ameliorated MPP+- and LPS-induced mouse mesencephalic astrocytes damage. Accordingly, curcumin protects against MPP+- and LPS-induced cytotoxicities in the mouse mesencephalic astrocyte via inhibiting the CYP2E1 expression and activity.

  8. The α-cyclodextrin complex of the Moringa isothiocyanate suppresses lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells through Akt and p38 inhibition.

    Science.gov (United States)

    Giacoppo, Sabrina; Rajan, Thangavelu Soundara; Iori, Renato; Rollin, Patrick; Bramanti, Placido; Mazzon, Emanuela

    2017-06-01

    In the last decades, a growing need to discover new compounds for the prevention and treatment of inflammatory diseases has led researchers to consider drugs derived from natural products as a valid option in the treatment of inflammation-associated disorders. The purpose of the present study was to investigate the anti-inflammatory effects of a new formulation of Moringa oleifera-derived 4-(α-L-rhamnopyranosyloxy)benzyl isothiocyanate as a complex with alpha-cyclodextrin (moringin + α-CD) on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells, a common model used for inflammation studies. In buffered/aqueous solution, the moringin + α-CD complex has enhanced the water solubility and stability of this isothiocyanate by forming a stable inclusion system. Our results showed that moringin + α-CD inhibits the production of inflammatory mediators in LPS-stimulated macrophages by down-regulation of pro-inflammatory cytokines (TNF-α and IL-1β), by preventing IκB-α phosphorylation, translocation of the nuclear factor-κB (NF-κB), and also via the suppression of Akt and p38 phosphorylation. In addition, as a consequence of upstream inhibition of the inflammatory pathway following treatment with moringin + α-CD, the modulation of the oxidative stress (results focused on the expression of iNOS and nitrotyrosine) and apoptotic pathway (Bax and Bcl-2) was demonstrated. Therefore, moringin + α-CD appears to be a new relevant helpful tool to use in clinical practice for inflammation-associated disorders.

  9. Polymeric proanthocyanidins from Sicilian pistachio (Pistacia vera L.) nut extract inhibit lipopolysaccharide-induced inflammatory response in RAW 264.7 cells.

    Science.gov (United States)

    Gentile, C; Allegra, M; Angileri, F; Pintaudi, A M; Livrea, M A; Tesoriere, L

    2012-04-01

    Positive effects of pistachio nut consumption on plasma inflammatory biomarkers have been described; however, little is known about molecular events associated with these effects. We studied the anti-inflammatory activity of a hydrophilic extract from Sicilian Pistacia L. (HPE) in a macrophage model and investigated bioactive components relevant to the observed effects. HPE oligomer/polymer proanthocyanidin fractions were isolated by adsorbance chromatography, and components quantified as anthocyanidins after acidic hydrolysis. Isoflavones were measured by gradient elution HPLC analysis. RAW 264.7 murine macrophages were pre-incubated with either HPE (1- to 20-mg fresh nut equivalents) or its isolated components for 1 h, then washed before stimulating with lipopolysaccharide (LPS) for 24 h. Cell viability and parameters associated with Nuclear Factor-κB (NF-κB) activation were assayed according to established methods including ELISA, Western blot, or cytofluorimetric analysis. HPE suppressed nitric oxide (NO) and tumor necrosis factor-α (TNF-α) production and inducible NO-synthase levels dose dependently, whereas inhibited prostaglandin E2 (PGE2) release and decreased cyclo-oxygenase-2 content, the lower the HPE amount the higher the effect. Cytotoxic effects were not observed. HPE also caused a dose-dependent decrease in intracellular reactive oxygen species and interfered with the NF-κB activation. Polymeric proanthocyanidins, but not isoflavones, at a concentration comparable with their content in HPE, inhibited NO, PGE2, and TNF-α formation, as well as activation of IκB-α. Oligomeric proanthocyanidins showed only minor effects. Our results provide molecular evidence of anti-inflammatory activity of pistachio nut and indicate polymeric proanthocyanidins as the bioactive components. The mechanism may involve the redox-sensitive transcription factor NF-κB. Potential effects associated with pistachio nut consumption are discussed in terms of the

  10. Picfeltarraenin IA inhibits lipopolysaccharide-induced inflammatory cytokine production by the nuclear factor-κB pathway in human pulmonary epithelial A549 cells.

    Science.gov (United States)

    Shi, Rong; Wang, Qing; Ouyang, Yang; Wang, Qian; Xiong, Xudong

    2016-02-01

    The present study aimed to investigate the effect of picfeltarraenin IA (IA) on respiratory inflammation by analyzing its effect on interleukin (IL)-8 and prostaglandin E2 (PGE2) production. The expression of cyclooxygenase 2 (COX2) in human pulmonary adenocarcinoma epithelial A549 cells in culture was also examined. Human pulmonary epithelial A549 cells and the human monocytic leukemia THP-1 cell line were used in the current study. Cell viability was measured using a methylthiazol tetrazolium assay. The production of IL-8 and PGE2 was investigated using an enzyme-linked immunosorbent assay. The expression of COX2 and nuclear factor-κB (NF-κB)-p65 was examined using western blot analysis. Treatment with lipopolysaccharide (LPS; 10 µg/ml) resulted in the increased production of IL-8 and PGE2, and the increased expression of COX2 in the A549 cells. Furthermore, IA (0.1-10 µmol/l) significantly inhibited PGE2 production and COX2 expression in cells with LPS-induced IL-8, in a concentration-dependent manner. The results suggested that IA downregulates LPS-induced COX2 expression, and inhibits IL-8 and PGE2 production in pulmonary epithelial cells. Additionally, IA was observed to suppress the expression of COX2 in THP-1 cells, and also to regulate the expression of COX2 via the NF-κB pathway in the A549 cells, but not in the THP-1 cells. These results indicate that IA regulates LPS-induced cytokine release in A549 cells via the NF-κB pathway.

  11. Oryza sativa (Rice) Hull Extract Inhibits Lipopolysaccharide-Induced Inflammatory Response in RAW264.7 Macrophages by Suppressing Extracellular Signal-regulated Kinase, c-Jun N-terminal Kinase, and Nuclear Factor-κB Activation.

    Science.gov (United States)

    Ha, Sang Keun; Sung, Jeehye; Choi, Inwook; Kim, Yoonsook

    2016-01-01

    Rice ( Oryza sativa ) is a major cereal crop in many Asian countries and an important staple food source. Rice hulls have been reported to possess antioxidant activities. In this study, we evaluated the antiinflammatory effects of rice hull extract and associated signal transduction mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that rice hull extract inhibited nitric oxide (NO) and prostaglandin E 2 by suppressing the expression of inducible NO synthase and cyclooxygenase-2, respectively. The release of interleukin-1β and tumor necrosis factor-α was also reduced in a dose-dependent manner. Furthermore, rice hull extract attenuated the activation of nuclear factor-kappa B (NF-κB), as well as the phosphorylation of mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), in LPS-stimulated RAW264.7 cells. This suggests that rice hull extract decreases the production of inflammatory mediators by downregulating ERK and JNK and the NF-κB signal pathway in RAW 264.7 cells. Rice hull extract inhibits the lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages.Rice hull extract inhibited nitric oxide and prostaglandin E 2 by suppressing the expression of inducible NO synthase and cyclooxygenase-2, respectively.Rice hull extract exerted anti-inflammatory effect through inhibition of nuclear factor-kappa B, extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways.Rice hull extract may provide a potential therapeutic approach for inflammatory diseases. Abbreviations used: COX-2: cyclooxygenase-2, ERK: extracellular signal-regulated kinase, IκB: inhibitory kappa B, IL-1β: interleukin-1β, iNOS: inducible NO synthase, JNK: c-Jun N-terminal kinase, LPS: lipopolysaccharide, MAPKs: mitogen-activated protein kinases, NF-κB: nuclear factor-κB, NO: nitric oxide, PGE2: prostaglandin E2, RHE: rice hull extract, ROS: reactive oxygen species

  12. Ruscogenin inhibits lipopolysaccharide-induced acute lung injury in mice: involvement of tissue factor, inducible NO synthase and nuclear factor (NF)-κB.

    Science.gov (United States)

    Sun, Qi; Chen, Ling; Gao, Mengyu; Jiang, Wenwen; Shao, Fangxian; Li, Jingjing; Wang, Jun; Kou, Junping; Yu, Boyang

    2012-01-01

    Acute lung injury is still a significant clinical problem with a high mortality rate and there are few effective therapies in clinic. Here, we studied the inhibitory effect of ruscogenin, an anti-inflammatory and anti-thrombotic natural product, on lipopolysaccharide (LPS)-induced acute lung injury in mice basing on our previous studies. The results showed that a single oral administration of ruscogenin significantly decreased lung wet to dry weight (W/D) ratio at doses of 0.3, 1.0 and 3.0 mg/kg 1 h prior to LPS challenge (30 mg/kg, intravenous injection). Histopathological changes such as pulmonary edema, coagulation and infiltration of inflammatory cells were also attenuated by ruscogenin. In addition, ruscogenin markedly decreased LPS-induced myeloperoxidase (MPO) activity and nitrate/nitrite content, and also downregulated expression of tissue factor (TF), inducible NO synthase (iNOS) and nuclear factor (NF)-κB p-p65 (Ser 536) in the lung tissue at three doses. Furthermore, ruscogenin reduced plasma TF procoagulant activity and nitrate/nitrite content in LPS-induced ALI mice. These findings confirmed that ruscogenin significantly attenuate LPS-induced acute lung injury via inhibiting expressions of TF and iNOS and NF-κB p65 activation, indicating it as a potential therapeutic agent for ALI or sepsis. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Pre-treatment with Toll-like receptor 4 antagonist inhibits lipopolysaccharide-induced preterm uterine contractility, cytokines, and prostaglandins in rhesus monkeys

    Science.gov (United States)

    Adams Waldorf, Kristina M.; Persing, David; Novy, Miles J.; Sadowsky, Drew W.; Gravett, Michael G.

    2009-01-01

    Intra-uterine infection, which occurs in the majority of early preterm births, triggers an immune response culminating in preterm labor. We hypothesized that blockade of lipopolysaccharide (LPS)-induced immune responses by a Toll-like receptor 4 antagonist (TLR4A) would prevent elevations in amniotic fluid (AF) cytokines, prostaglandins, and uterine contractility. Chronically catheterized rhesus monkeys at 128-147 days gestation received intra-amniotic infusions of either: 1) saline (n=6), 2) LPS (0.15-10μg; n=4), or 3) TLR4A pre-treatment with LPS (10 μg) one hour later (n=4). AF cytokines, prostaglandins, and uterine contractility were compared using oneway ANOVA with Bonferroni-adjusted pairwise comparisons. Compared to saline controls, LPS induced significant elevations in AF IL-8, TNF-α, PGE2, PGF2α, and uterine contractility (p<0.05). In contrast, TLR4A pre-treatment inhibited LPS-induced uterine activity and was associated with significantly lower AF IL-8, TNF-α, PGE2, and PGF2α versus LPS alone (p<0.05). Toll-like receptor antagonists, together with antibiotics, may delay or prevent infection-associated preterm birth. PMID:18187405

  14. Mangiferin inhibits lipopolysaccharide-induced production of interleukin-6 in human oral epithelial cells by suppressing toll-like receptor signaling.

    Science.gov (United States)

    Li, Hao; Wang, Qi; Chen, Xinmin; Ding, Yi; Li, Wei

    2016-11-01

    Oral epithelial cells have currently been found to play an important role in inflammatory modulation in periodontitis. Mangiferin is a natural glucosylxanthone with anti-inflammatory activity. The aim of this study was to investigate the regulatory effect of mangiferin on lipopolysaccharide (LPS)-induced production of proinflammatory cytokine interleukin-6 (IL-6) in oral epithelial cells and the underlying mechanisms. The levels of LPS-induced IL-6 production in OKF6/TERT-2 oral keratinocytes were detected using enzyme-linked immunosorbent assay (ELISA). The expression of Toll-like receptor (TLR) 2 and TLR4 was determined using western blot analysis. And the phosphorylation of TLR downstream nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) was examined using cell-based protein phosphorylation ELISA kits. We found that mangiferin reduced LPS-upregulated IL-6 production in OKF6/TERT-2 cells. Additionally, mangiferin inhibited LPS-induced TLR2 and TLR4 overexpression, and suppressed the phosphorylation of NF-κB, p38 MAPK and JNK. Moreover, mangiferin repressed IL-6 production and TLR signaling activation in a dose-dependent manner after 24h treatment. Mangiferin decreases LPS-induced production of IL-6 in human oral epithelial cells by suppressing TLR signaling, and this glucosylxanthone may have potential for the treatment of periodontitis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Bee Venom Inhibits Porphyromonas gingivalis Lipopolysaccharides-Induced Pro-Inflammatory Cytokines through Suppression of NF-κB and AP-1 Signaling Pathways.

    Science.gov (United States)

    Kim, Woon-Hae; An, Hyun-Jin; Kim, Jung-Yeon; Gwon, Mi-Gyeong; Gu, Hyemin; Park, Jae-Bok; Sung, Woo Jung; Kwon, Yong-Chul; Park, Kyung-Duck; Han, Sang Mi; Park, Kwan-Kyu

    2016-11-10

    Periodontitis is a chronic inflammatory disease that leads to destruction of tooth supporting tissues. Porphyromonas gingivalis ( P. gingivalis ), especially its lipopolysaccharides (LPS), is one of major pathogens that cause periodontitis. Bee venom (BV) has been widely used as a traditional medicine for various diseases. Previous studies have demonstrated the anti-inflammatory, anti-bacterial effects of BV. However, a direct role and cellular mechanism of BV on periodontitis-like human keratinocytes have not been explored. Therefore, we investigated the anti-inflammatory mechanism of BV against P. gingivalis LPS (PgLPS)-induced HaCaT human keratinocyte cell line. The anti-inflammatory effect of BV was demonstrated by various molecular biological methods. The results showed that PgLPS increased the expression of Toll-like receptor (TLR)-4 and pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and interferon (IFN)-γ. In addition, PgLPS induced activation of the signaling pathways of inflammatory cytokines-related transcription factors, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1). BV effectively inhibited those pro-inflammatory cytokines through suppression of NF-κB and AP-1 signaling pathways. These results suggest that administration of BV attenuates PgLPS-induced inflammatory responses. Furthermore, BV may be a useful treatment to anti-inflammatory therapy for periodontitis.

  16. Neocryptotanshinone inhibits lipopolysaccharide-induced inflammation in RAW264.7 macrophages by suppression of NF-κB and iNOS signaling pathways

    Directory of Open Access Journals (Sweden)

    Chuanhong Wu

    2015-07-01

    Full Text Available Neocryptotanshinone (NCTS is a natural product isolated from traditional Chinese herb Salvia miltiorrhiza Bunge. In this study, we investigated its anti-inflammatory effects in lipopolysaccharide (LPS-stimulated mouse macrophage (RAW264.7 cells. MTT results showed that NCTS partly reversed LPS-induced cytotoxicity. Real-time PCR results showed that NCTS suppressed LPS-induced mRNA expression of inflammatory cytokines, including tumor necrosis factor α (TNFα, interleukin-6 (IL-6 and interleukin-1β (IL-1β. Moreover, NCTS could decrease LPS-induced nitric oxide (NO production. Western blotting results showed that NCTS could down-regulate LPS-induced expression of inducible nitric oxide synthase (iNOS, p-IκBα, p-IKKβ and p-NF-κB p65 without affecting cyclooxygenase-2 (COX-2. In addition, NCTS inhibited LPS-induced p-NF-κB p65 nuclear translocation. In conclusion, these data demonstrated that NCTS showed anti-inflammatory effect by suppression of NF-κB and iNOS signaling pathways.

  17. Oenothera laciniata inhibits lipopolysaccharide induced production of nitric oxide, prostaglandin E2, and proinflammatory cytokines in RAW264.7 macrophages.

    Science.gov (United States)

    Yoon, Weon-Jong; Ham, Young Min; Yoo, Byoung-Sam; Moon, Ji-Young; Koh, Jaesook; Hyun, Chang-Gu

    2009-04-01

    We elucidated the pharmacological and biological effects of Oenothera laciniata extracts on the production of inflammatory mediators in macrophages. The CH(2)Cl(2) fraction of O. laciniata extract effectively inhibited LPS-induced NO, PGE(2), and proinflammatory cytokine production in RAW264.7 cells. These inhibitory effects of the CH(2)Cl(2) fraction of O. laciniata were accompanied by decreases in the expression of iNOS and COX-2 proteins and iNOS, COX-2, TNF-alpha, IL-1beta, and IL-6 mRNA. Asiatic acid and quercetin were present in the HPLC fingerprint of the O. laciniata extract. We tested the potential application of O. laciniata extract as a cosmetic material by performing primary skin irritation tests. In New Zealand white rabbits, primary irritation tests revealed that application of O. laciniata extracts (1%) did not induce erythema or edema formation. Human skin primary irritation tests were performed on the normal skin (upper back) of 30 volunteers to determine if any material in O. laciniata extracts had irritation or sensitization potential. In these assays, O. laciniata extracts did not induce any adverse reactions. Based on these results, we suggest that O. laciniata extracts be considered possible anti-inflammatory candidates for topical application.

  18. NCX 4040, a nitric oxide-donating aspirin derivative, inhibits Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    Science.gov (United States)

    Choi, Eun-Young; Choe, So-Hui; Hyeon, Jin-Yi; Park, Hae Ryoun; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2015-12-05

    In this study, the effects and underlying mechanisms of NCX 4040, a nitric oxide (NO)-donating aspirin derivative, on the production of proinflammatory mediators were examined using murine macrophages exposed to lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in the etiology of periodontal disease. NCX 4040 significantly reduced P. intermedia LPS-induced production of inducible NO synthase (iNOS)-derived NO, IL-1β and IL-6 as well as their mRNA expression in RAW264.7 cells. Notably, NCX 4040 was much more effective than the parental compound aspirin in reducing LPS-induced production of inflammatory mediators. NCX 4040 induced the expression of heme oxygenase-1 (HO-1) in cells treated with P. intermedia LPS, and the suppressive effect of NCX 4040 on LPS-induced NO production was significantly reversed by SnPP, a competitive HO-1 inhibitor. NCX 4040 did not influence LPS-induced phosphorylation of JNK and p38. IκB-α degradation as well as nuclear translocation and DNA-binding activities of NF-κB p65 and p50 subunits induced by P. intermedia LPS were significantly reduced by NCX 4040. Besides, LPS-induced phosphorylation of STAT1 and STAT3 was significantly down-regulated by NCX 4040. Further, NCX 4040 elevated the SOCS1 mRNA in cells stimulated with LPS. This study indicates that NCX 4040 inhibits P. intermedia LPS-induced production of NO, IL-1β and IL-6 in murine macrophages through anti-inflammatory HO-1 induction and suppression of NF-κB, STAT1 and STAT3 activation, which is associated with the activation of SOCS1 signaling. NCX 4040 could potentially be a promising tool in the treatment of periodontal disease, although further studies are required to verify this. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Inhibition of Phosphodiesterase 4 by FCPR03 Alleviates Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice: Involvement of p38 and JNK Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Hui Yu

    2018-02-01

    Full Text Available Inflammatory responses induced by peripheral administration of lipopolysaccharide (LPS triggers depressive-like behavioral syndrome in rodents. Inhibition of phosphodiesterase 4 (PDE4 produces a robust anti-inflammatory effect in inflammatory cells. Unfortunately, archetypal PDE4 inhibitors cause intolerable gastrointestinal side-effects, such as vomiting and nausea. N-isopropyl-3-(cyclopropylmethoxy-4-difluoromethoxy benzamide (FCPR03 is a novel, selective PDE4 inhibitor with little, or no, emetic potency. Our previous studies show that FCPR03 is effective in attenuating neuroinflammation in mice treated with LPS. However, whether FCPR03 could exert antidepressant-like effect induced by LPS is largely unknown. In the present study, mice injected intraperitoneally (i.p. with LPS was established as an in vivo animal model of depression. The antidepressant-like activities of FCPR03 were evaluated using a tail suspension test, forced swimming test, and sucrose preference test. We demonstrated that administration of FCPR03 (1 mg/kg produced antidepressant-like effects in mice challenged by LPS, as evidenced by decreases in the duration of immobility in the forced swim and tail suspension tests, while no significant changes in locomotor activity were observed. FCPR03 also increased sucrose preference in mice treated with LPS. In addition, treatment with FCPR03 abolished the downregulation of brain-derived neurotrophic factor induced by LPS and decreased the level of corticosterone in plasma. Meanwhile, periphery immune challenge by LPS induced enhanced phosphorylation of p38-mitogen activated protein kinase (p38 and c-Jun N-terminal kinase (JNK in both the cerebral cortex and hippocampus in mice. Interestingly, treatment with FCPR03 significantly blocked the role of LPS and reduced the levels of phosphorylated p38 and JNK. Collectively, these results indicate that FCPR03 shows antidepressant-like effects in mice challenged by LPS, and the p38/JNK

  20. SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages

    International Nuclear Information System (INIS)

    Lee, Ae Sin; Jung, Yu Jin; Kim, Dal; Nguyen-Thanh, Tung; Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang; Kim, Won

    2014-01-01

    Highlights: • Knockout of SIRT2 attenuates lipopolysaccharide-induced iNOS expression. • Lipopolysaccharide-induced NO production is decreased in SIRT2 KO macrophage. • SIRT2 deficiency suppresses lipopolysaccharide-induced ROS production in macrophage. • M1-macrophage related factors are decreased in SIRT2 deficient cells. • SIRT2 deficiency decreases lipopolysaccharide-induced activation of NFκB. - Abstract: Introduction: SIRT2 is a NAD(+)-dependent deacetylases and associated with numerous processes such as infection, carcinogenesis, DNA damage and cell cycle regulation. However, the role of SIRT2 in inflammatory process in macrophage remains unclear. Materials and methods: In the present study, we have evaluated the regulatory effects of SIRT2 in lipopolysaccharide (LPS)-stimulated macrophages isolated from SIRT2 knockout (KO) and wild type (WT) mice or Raw264.7 macrophage cells. As inflammatory parameters, expression of inducible nitric oxide synthase (iNOS), the productions of nitric oxide, reactive oxygen species (ROS) and M1-macrophage-related factors were evaluated. We also examined the effects of SIRT2 on activation of nuclear factor-kappaB (NFκB) signaling. Results: SIRT2 deficiency inhibits LPS-induced iNOS mRNA and protein expression in bone marrow derived macrophages. SIRT2-siRNA transfection also suppressed LPS-induced iNOS expression in Raw264.7 macrophage cells. Bone marrow derived macrophages isolated from SIRT2 KO mice produced lower nitric oxide and expressed lower levels of M1-macrophage related markers including iNOS and CD86 in response to LPS than WT mice. Decrease of SIRT2 reduced the LPS-induced reactive oxygen species production. Deficiency of SIRT2 resulted in inhibition of NFκB activation through reducing the phosphorylation and degradation of IκBα. The phosphorylation and nuclear translocation of p65 was significantly decreased in SIRT2-deficient macrophages after LPS stimulation. Discussion: Our data suggested that

  1. SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ae Sin; Jung, Yu Jin; Kim, Dal; Nguyen-Thanh, Tung [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kang, Kyung Pyo [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Lee, Sik [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Park, Sung Kwang [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Kim, Won, E-mail: kwon@jbnu.ac.kr [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of)

    2014-08-08

    Highlights: • Knockout of SIRT2 attenuates lipopolysaccharide-induced iNOS expression. • Lipopolysaccharide-induced NO production is decreased in SIRT2 KO macrophage. • SIRT2 deficiency suppresses lipopolysaccharide-induced ROS production in macrophage. • M1-macrophage related factors are decreased in SIRT2 deficient cells. • SIRT2 deficiency decreases lipopolysaccharide-induced activation of NFκB. - Abstract: Introduction: SIRT2 is a NAD(+)-dependent deacetylases and associated with numerous processes such as infection, carcinogenesis, DNA damage and cell cycle regulation. However, the role of SIRT2 in inflammatory process in macrophage remains unclear. Materials and methods: In the present study, we have evaluated the regulatory effects of SIRT2 in lipopolysaccharide (LPS)-stimulated macrophages isolated from SIRT2 knockout (KO) and wild type (WT) mice or Raw264.7 macrophage cells. As inflammatory parameters, expression of inducible nitric oxide synthase (iNOS), the productions of nitric oxide, reactive oxygen species (ROS) and M1-macrophage-related factors were evaluated. We also examined the effects of SIRT2 on activation of nuclear factor-kappaB (NFκB) signaling. Results: SIRT2 deficiency inhibits LPS-induced iNOS mRNA and protein expression in bone marrow derived macrophages. SIRT2-siRNA transfection also suppressed LPS-induced iNOS expression in Raw264.7 macrophage cells. Bone marrow derived macrophages isolated from SIRT2 KO mice produced lower nitric oxide and expressed lower levels of M1-macrophage related markers including iNOS and CD86 in response to LPS than WT mice. Decrease of SIRT2 reduced the LPS-induced reactive oxygen species production. Deficiency of SIRT2 resulted in inhibition of NFκB activation through reducing the phosphorylation and degradation of IκBα. The phosphorylation and nuclear translocation of p65 was significantly decreased in SIRT2-deficient macrophages after LPS stimulation. Discussion: Our data suggested that

  2. Inhibition of Lipopolysaccharide-Induced Neuroinflammatory Events ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research October 2014; 13 (10): 1615-1620. ISSN: 1596-5996 ... LPS-induced excessive production of inflammatory mediator such as iNOS was also ... several studies have reported antioxidant, antiallergic ...

  3. Isorhamnetin inhibits Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages via anti-inflammatory heme oxygenase-1 induction and inhibition of nuclear factor-κB and signal transducer and activator of transcription 1 activation.

    Science.gov (United States)

    Jin, J Y; Choi, E Y; Park, H R; Choi, J I; Choi, I S; Kim, S J

    2013-12-01

    Interleukin-6 (IL-6) is a key proinflammatory cytokine that has been considered to be important in the pathogenesis of periodontal disease. Therefore, host-modulatory agents directed at inhibiting IL-6 appear to be beneficial in terms of attenuating periodontal disease progression and potentially improving disease susceptibility. In the current study, we investigated the effect of the flavonoid isorhamnetin on the production of IL-6 in murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Lipopolysaccharide from P. intermedia ATCC 25611 was isolated using the standard hot phenol-water method. Culture supernatants were collected and assayed for IL-6. We used real-time PCR to quantify IL-6 and heme oxygenase-1 (HO-1) mRNA expression. The expression of HO-1 protein and the levels of signaling proteins were monitored using immunoblot analyses. The DNA-binding activity of nuclear factor-κB (NF-κB) was analyzed using ELISA-based assay kits. Isorhamnetin significantly down-regulated P. intermedia LPS-induced production of IL-6 as well as its mRNA expression in RAW264.7 cells. Isorhamnetin up-regulated the expression of HO-1 at both gene transcription and translation levels in cells stimulated with P. intermedia LPS. In addition, inhibition of HO-1 activity by tin protoporphyrin IX blocked the inhibitory effect of isorhamnetin on IL-6 production. Isorhamnetin failed to prevent LPS from activating either c-Jun N-terminal kinase or p38 pathways. Isorhamnetin did not inhibit NF-κB transcriptional activity at the level of inhibitory κB-α degradation. Isorhamnetin suppressed NF-κB signaling through inhibition of nuclear translocation and DNA binding activity of NF-κB p50 subunit and attenuated signal transducer and activator of transcription 1 signaling. Although further research is required to clarify the detailed mechanism of action, we propose

  4. Inhibition of lipopolysaccharide-induced proinflammatory responses by Buddleja officinalis extract in BV-2 microglial cells via negative regulation of NF-kB and ERK1/2 signaling.

    Science.gov (United States)

    Oh, Won-Jun; Jung, Uhee; Eom, Hyun-Soo; Shin, Hee-June; Park, Hae-Ran

    2013-07-31

    Buddleja officinalis has been traditionally used in the supportive treatment of inflammatory and neuronal diseases in Korea and China. Although several reports have shown the anti-inflammatory effects of Buddleja officinalis, the anti-neuroinflammatory effect has remained unclear. In this study, we aimed to investigate the inhibitory effects of flower buds of B. officinalis Maximowicz water extract (BOWE) on LPS-induced inflammatory processes in BV-2 microglial cells. BOWE dose-dependently inhibited the production of nitric oxide as well as iNOS mRNA expression. Moreover, BOWE prevented IL-1β and IL-6 mRNA expression. However, BOWE had no effect on LPS-induced COX-2 or TNF-a mRNA expression. The extract also had no effect on LPS-stimulated p38 MAPK, JNK, and c-Jun phosphorylation, whereas ERK1/2 phosphorylation was strongly inhibited by BOWE. BOWE also inhibited the LPS-induced degradation of IkB-α, and LPS-induced phosphorylation of p65 NF-kB protein. These data indicate that BOWE inhibited the nitric oxide production and pro-inflammatory gene expression in BV-2 microglial cells, possibly through a negative regulation of the NF-kB and ERK1/2 pathways. Further identification of the direct target molecule(s) of BOWE is required to support its use as an anti-neuroinflammatory agent against the neurodegenerative disorders.

  5. Inhibition of Lipopolysaccharide-Induced Proinflammatory Responses by Buddleja officinalis Extract in BV-2 Microglial Cells via Negative Regulation of NF-kB and ERK1/2 Signaling

    Directory of Open Access Journals (Sweden)

    Hae-Ran Park

    2013-07-01

    Full Text Available Buddleja officinalis has been traditionally used in the supportive treatment of inflammatory and neuronal diseases in Korea and China. Although several reports have shown the anti-inflammatory effects of Buddleja officinalis, the anti-neuroinflammatory effect has remained unclear. In this study, we aimed to investigate the inhibitory effects of flower buds of B. officinalis Maximowicz water extract (BOWE on LPS-induced inflammatory processes in BV-2 microglial cells. BOWE dose-dependently inhibited the production of nitric oxide as well as iNOS mRNA expression. Moreover, BOWE prevented IL-1β and IL-6 mRNA expression. However, BOWE had no effect on LPS-induced COX-2 or TNF-a mRNA expression. The extract also had no effect on LPS-stimulated p38 MAPK, JNK, and c-Jun phosphorylation, whereas ERK1/2 phosphorylation was strongly inhibited by BOWE. BOWE also inhibited the LPS-induced degradation of IkB-α, and LPS-induced phosphorylation of p65 NF-kB protein. These data indicate that BOWE inhibited the nitric oxide production and pro-inflammatory gene expression in BV-2 microglial cells, possibly through a negative regulation of the NF-kB and ERK1/2 pathways. Further identification of the direct target molecule(s of BOWE is required to support its use as an anti-neuroinflammatory agent against the neurodegenerative disorders.

  6. Anti-Inflammatory Effect of Methylpenicinoline from a Marine Isolate of Penicillium sp. (SF-5995: Inhibition of NF-κB and MAPK Pathways in Lipopolysaccharide-Induced RAW264.7 Macrophages and BV2 Microglia

    Directory of Open Access Journals (Sweden)

    Dong-Cheol Kim

    2014-11-01

    Full Text Available In the course of a search for anti-inflammatory metabolites from marine-derived fungi, methylpenicinoline (1 was isolated from a marine isolate of Penicillin sp. Compound 1 inhibited lipopolysaccharide (LPS-stimulated nitric oxide (NO production by suppressing the expression of inducible NO synthase (iNOS in RAW264.7 macrophages and BV2 microglia. It also attenuated prostaglandin E2 (PGE2 production by suppressing cyclooxygenase-2 (COX-2 expression in a concentration-dependent manner (from 10 μM to 80 μM without affecting cell viability. In addition, compound 1 reduced the production of the pro-inflammatory cytokine interleukin-1β (IL-1β. In a further study designed to elucidate the mechanism of its anti-inflammatory effects, compound 1 was shown to block nuclear factor-kappa B (NF-κB activation in LPS-induced RAW264.7 macrophages and BV2 microglia by inhibiting the phosphorylation of inhibitor kappa B-α (IκB-α, thereby suppressing the nuclear translocation of NF-κB dimers, namely p50 and p65, that are known to be crucial molecules associated with iNOS and COX-2 expression. In addition, compound 1 inhibited the activation of mitogen-activated protein kinase (MAPK pathways. Taken together, the results suggest that compound 1 might be a valuable therapeutic agent for the treatment of anti-inflammatory and anti-neuroinflammatory diseases.

  7. Pyrroloquinoline quinone (PQQ inhibits lipopolysaccharide induced inflammation in part via downregulated NF-κB and p38/JNK activation in microglial and attenuates microglia activation in lipopolysaccharide treatment mice.

    Directory of Open Access Journals (Sweden)

    Chongfei Yang

    Full Text Available Therapeutic strategies designed to inhibit the activation of microglia may lead to significant advancement in the treatment of most neurodegenerative diseases. Pyrroloquinoline quinone (PQQ is a naturally occurring redox cofactor that acts as an essential nutrient, antioxidant, and has been reported to exert potent immunosuppressive effects. In the present study, the anti-inflammatory effects of PQQ was investigated in LPS treated primary microglia cells. Our observations showed that pretreatment with PQQ significantly inhibited the production of NO and PGE2 and suppressed the expression of pro-inflammatory mediators such as iNOS, COX-2, TNF-a, IL-1b, IL-6, MCP-1 and MIP-1a in LPS treated primary microglia cells. The nuclear translocation of NF-κB and the phosphorylation level of p65, p38 and JNK MAP kinase pathways were also inhibited by PQQ in LPS stimulated primary microglia cells. Further a systemic LPS treatment acute inflammation murine brain model was used to study the suppressive effects of PQQ against neuroinflammation in vivo. Mice treated with PQQ demonstrated marked attenuation of neuroinflammation based on Western blotting and immunohistochemistry analysis of Iba1-against antibody in the brain tissue. Indicated that PQQ protected primary cortical neurons against microglia-mediated neurotoxicity. These results collectively suggested that PQQ might be a promising therapeutic agent for alleviating the progress of neurodegenerative diseases associated with microglia activation.

  8. Preventive Effects of Velvet Antler (Cervus elaphus against Lipopolysaccharide-Induced Acute Lung Injury in Mice by Inhibiting MAPK/NF-κB Activation and Inducing AMPK/Nrf2 Pathways

    Directory of Open Access Journals (Sweden)

    Jui-Shu Chang

    2018-01-01

    Full Text Available Velvet antler (Cervus elaphus is a typical traditional animal medicine. It is considered to have various pharmacological effects including stimulation of the immune system, increase in the physical strength, and enhancement of sexual function. This paper aims to investigate the aqueous extract of velvet antler (AVA in the mouse models of LPS-induced ALI. Inhibition of NO, TNF-α, IL-1β, IL-6, and IL-10 productions contributes to the attenuation of LPS-induced lung inflammation by AVA. A 5-day pretreatment of AVA prevented histological alterations and enhanced antioxidant enzyme activity in lung tissues. AVA significantly reduced the material (total number of cells and proteins in the BALF. Western blot analysis revealed that the expression of iNOS and COX-2 and phosphorylation of IκB-α and MAPKs proteins are blocked in LPS-stimulated macrophages as well as LPS-induced lung injury in mice. Consistent with this concept, the phosphorylation of CaMKKβ, LKB1, AMPK, Nrf2, and HO-1 was activated after AVA treatment. The results from this study indicate AVA has anti-inflammatory effects in vivo and AVA is a potential model for the development of health food. In addition, its pathways may be at least partially associated with inhibiting MAPK/NF-κB activation and upregulating AMPK/Nrf2 pathways and the regulation of antioxidant enzyme activity.

  9. 14-3-3γ Regulates Lipopolysaccharide-Induced Inflammatory Responses and Lactation in Dairy Cow Mammary Epithelial Cells by Inhibiting NF-κB and MAPKs and Up-Regulating mTOR Signaling

    Directory of Open Access Journals (Sweden)

    Lixin Liu

    2015-07-01

    Full Text Available As a protective factor for lipopolysaccharide (LPS-induced injury, 14-3-3γ has been the subject of recent research. Nevertheless, whether 14-3-3γ can regulate lactation in dairy cow mammary epithelial cells (DCMECs induced by LPS remains unknown. Here, the anti-inflammatory effect and lactation regulating ability of 14-3-3γ in LPS-induced DCMECs are investigated for the first time, and the molecular mechanisms responsible for their effects are explored. The results of qRT-PCR showed that 14-3-3γ overexpression significantly inhibited the mRNA expression of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, interleukin-1β (IL-1β and inducible nitric oxide synthase (iNOS. Enzyme-linked immunosorbent assay (ELISA analysis revealed that 14-3-3γ overexpression also suppressed the production of TNF-α and IL-6 in cell culture supernatants. Meanwhile, CASY-TT Analyser System showed that 14-3-3γ overexpression clearly increased the viability and proliferation of cells. The results of kit methods and western blot analysis showed that 14-3-3γ overexpression promoted the secretion of triglycerides and lactose and the synthesis of β-casein. Furthermore, the expression of genes relevant to nuclear factor-κB (NF-κB and mitogen-activated protein kinase (MAPKs and lactation-associated proteins were assessed by western blot, and the results suggested that 14-3-3γ overexpression inactivated the NF-κB and MAPK signaling pathways by down-regulating extracellular signal regulated protein kinase (ERK, p38 mitogen-activated protein kinase (p38MAPK and inhibitor of NF-κB (IκB phosphorylation levels, as well as by inhibiting NF-κB translocation. Meanwhile, 14-3-3γ overexpression enhanced the expression levels of β-casein, mammalian target of rapamycin (mTOR, ribosomal protein S6 kinase 1 (S6K1, serine/threonine protein kinase Akt 1 (AKT1, sterol regulatory element binding protein 1 (SREBP1 and peroxisome proliferator-activated receptor gamma

  10. Vitamin D inhibits lipopolysaccharide-induced inflammatory response potentially through the Toll-like receptor 4 signalling pathway in the intestine and enterocytes of juvenile Jian carp (Cyprinus carpio var. Jian).

    Science.gov (United States)

    Jiang, Jun; Shi, Dan; Zhou, Xiao-Qiu; Yin, Long; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Tang, Ling; Wu, Pei; Zhao, Ye

    2015-11-28

    The present study was conducted to investigate the anti-inflammatory effect of vitamin D both in juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and in enterocytes in vitro. In primary enterocytes, exposure to 10 mg lipopolysaccharide (LPS)/l increased lactate dehydrogenase activity in the culture medium (P<0·05) and resulted in a significant loss of cell viability (P<0·05). LPS exposure increased (P<0·05) the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8), which was decreased by pre-treatment with 1,25-dihydroxyvitamin D (1,25D3) in a dose-dependent manner (P<0·05). Further results showed that pre-treatment with 1,25D3 down-regulated Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88) and NF-κB p65 mRNA expression (P<0·05), suggesting potential mechanisms against LPS-induced inflammatory response. In vivo, intraperitoneal injection of LPS significantly increased TNF-α, IL-1β, IL-6 and IL-8 mRNA expression in the intestine of carp (P<0·05). Pre-treatment of fish with vitamin D3 protected the fish intestine from the LPS-induced increase of TNF-α, IL-1β, IL-6 and IL-8 mainly by downregulating TLR4, Myd88 and NF-κB p65 mRNA expression (P<0·05). These observations suggest that vitamin D could inhibit LPS-induced inflammatory response in juvenile Jian carp in vivo and in enterocytes in vitro. The anti-inflammatory effect of vitamin D is mediated at least in part by TLR4-Myd88 signalling pathways in the intestine and enterocytes of juvenile Jian carp.

  11. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China); Qiao, Juan, E-mail: qjuan@tsinghua.edu.cn [Department of Chemistry, Tsinghua University, Beijing 100084 (China); Lu, Yun, E-mail: luyun@tsinghua.edu.cn [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China)

    2016-02-13

    Highlights: • Chlorination is effective to reduce the inflammation inducing capacity of LPS in lung. • LAL-detected endotoxin activity is not correlated to the potency of inflammation induction. • Alkyl chain of LPS was chlorinated in chlorination process. • LPS aggregate size decreases after chlorination. - Abstract: Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies.

  12. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination.

    Science.gov (United States)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani; Qiao, Juan; Lu, Yun

    2016-02-13

    Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination

    International Nuclear Information System (INIS)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani; Qiao, Juan; Lu, Yun

    2016-01-01

    Highlights: • Chlorination is effective to reduce the inflammation inducing capacity of LPS in lung. • LAL-detected endotoxin activity is not correlated to the potency of inflammation induction. • Alkyl chain of LPS was chlorinated in chlorination process. • LPS aggregate size decreases after chlorination. - Abstract: Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies.

  14. A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation.

    Science.gov (United States)

    Ishibashi, Ryoichi; Takemoto, Minoru; Akimoto, Yoshihiro; Ishikawa, Takahiro; He, Peng; Maezawa, Yoshiro; Sakamoto, Kenichi; Tsurutani, Yuya; Ide, Shintaro; Ide, Kana; Kawamura, Harukiyo; Kobayashi, Kazuki; Tokuyama, Hirotake; Tryggvason, Karl; Betsholtz, Christer; Yokote, Koutaro

    2016-05-16

    Kidney diseases including diabetic nephropathy have become huge medical problems, although its precise mechanisms are still far from understood. In order to increase our knowledge about the patho-physiology of kidney, we have previously identified >300 kidney glomerulus-enriched transcripts through large-scale sequencing and microarray profiling of the mouse glomerular transcriptome. One of the glomerulus-specific transcripts identified was semaphorin 3G (Sema3G) which belongs to the semaphorin family. The aim of this study was to analyze both the in vivo and in vitro functions of Sema3G in the kidney. Sema3G was expressed in glomerular podocytes. Although Sema3G knockout mice did not show obvious glomerular defects, ultrastructural analyses revealed partially aberrant podocyte foot processes structures. When these mice were injected with lipopolysaccharide to induce acute inflammation or streptozotocin to induce diabetes, the lack of Sema3G resulted in increased albuminuria. The lack of Sema3G in podocytes also enhanced the expression of inflammatory cytokines including chemokine ligand 2 and interleukin 6. On the other hand, the presence of Sema3G attenuated their expression through the inhibition of lipopolysaccharide-induced Toll like receptor 4 signaling. Taken together, our results surmise that the Sema3G protein is secreted by podocytes and protects podocytes from inflammatory kidney diseases and diabetic nephropathy.

  15. Inhibitory Effects of Ketamine on Lipopolysaccharide-Induced Microglial Activation

    Directory of Open Access Journals (Sweden)

    Yi Chang

    2009-01-01

    Full Text Available Microglia activated in response to brain injury release neurotoxic factors including nitric oxide (NO and proinflammatory cytokines such as tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β. Ketamine, an anesthetic induction agent, is generally reserved for use in patients with severe hypotension or respiratory depression. In this study, we found that ketamine (100 and 250 μM concentration-dependently inhibited lipopolysaccharide (LPS-induced NO and IL-1β release in primary cultured microglia. However, ketamine (100 and 250 μM did not significantly inhibit the LPS-induced TNF-α production in microglia, except at the higher concentration (500 μM. Further study of the molecular mechanisms revealed that ketamine markedly inhibited extracellular signal-regulated kinase (ERK1/2 phosphorylation but not c-Jun N-terminal kinase or p38 mitogen-activated protein kinase stimulated by LPS in microglia. These results suggest that microglial inactivation by ketamine is at least partially due to inhibition of ERK1/2 phosphorylation.

  16. Agmatine attenuates stress- and lipopolysaccharide-induced fever in rats

    Science.gov (United States)

    Aricioglu, Feyza; Regunathan, Soundar

    2010-01-01

    Physiological stress evokes a number of responses, including a rise in body temperature, which has been suggested to be the result of an elevation in the thermoregulatory set point. This response seems to share similar mechanisms with infectious fever. The aim of the present study was to investigate the effect of agmatine on different models of stressors [(restraint and lipopolysaccaride (LPS)] on body temperature. Rats were either restrained for 4 h or injected with LPS, both of these stressors caused an increase in body temperature. While agmatine itself had no effect on body temperature, treatment with agmatine (20, 40, 80 mg/kg intraperitoneally) dose dependently inhibited stress- and LPS-induced hyperthermia. When agmatine (80 mg/kg) was administered 30 min later than LPS (500 μg/kg) it also inhibited LPS-induced hyperthermia although the effect became significant only at later time points and lower maximal response compared to simultaneous administration. To determine if the decrease in body temperature is associated with an anti-inflammatory effect of agmatine, the nitrite/nitrate levels in plasma was measured. Agmatine treatment inhibited LPS-induced production of nitrates dose dependently. As an endogenous molecule, agmatine has the capacity to inhibit stress- and LPS-induced increases in body temperature. PMID:15936786

  17. Lipopolysaccharide-induced acute renal failure in conscious rats

    DEFF Research Database (Denmark)

    Jonassen, Thomas E N; Graebe, Martin; Promeneur, Dominique

    2002-01-01

    In conscious, chronically instrumented rats we examined 1) renal tubular functional changes involved in lipopolysaccharide (LPS)-induced acute renal failure; 2) the effects of LPS on the expression of selected renal tubular water and sodium transporters; and 3) effects of milrinone......-alpha and lactate, inhibited the LPS-induced tachycardia, and exacerbated the acute LPS-induced fall in GFR. Furthermore, Ro-20-1724-treated rats were unable to maintain MAP. We conclude 1) PDE3 or PDE4 inhibition exacerbates LPS-induced renal failure in conscious rats; and 2) LPS treated rats develop an escape......, a phosphodiesterase type 3 (PDE3) inhibitor, and Ro-20-1724, a PDE4 inhibitor, on LPS-induced changes in renal function. Intravenous infusion of LPS (4 mg/kg b.wt. over 1 h) caused an immediate decrease in glomerular filtration rate (GFR) and proximal tubular outflow without changes in mean arterial pressure (MAP...

  18. Calcium hydroxide suppresses Porphyromonas endodontalis lipopolysaccharide-induced bone destruction.

    Science.gov (United States)

    Guo, J; Yang, D; Okamura, H; Teramachi, J; Ochiai, K; Qiu, L; Haneji, T

    2014-05-01

    Porphyromonas endodontalis and its main virulence factor, lipopolysaccharide (LPS), are associated with the development of periapical diseases and alveolar bone loss. Calcium hydroxide is commonly used for endodontic therapy. However, the effects of calcium hydroxide on the virulence of P. endodontalis LPS and the mechanism of P. endodontalis LPS-induced bone destruction are not clear. Calcium hydroxide rescued the P. endodontalis LPS-suppressed viability of MC3T3-E1 cells and activity of nuclear factor-κB (NF-κB) in these cells, resulting in the reduced expression of interleukin-6 and tumor necrosis factor-α. In addition, calcium hydroxide inhibited P. endodontalis LPS-induced osteoclastogenesis by decreasing the activities of NF-κB, p38, and ERK1/2 and the expression of nuclear factor of activated T-cell cytoplasmic 1 in RAW264.7 cells. Calcium hydroxide also rescued the P. endodontalis LPS-induced osteoclastogenesis and bone destruction in mouse calvaria. Taken together, our present results indicate that calcium hydroxide suppressed bone destruction by attenuating the virulence of P. endodontalis LPS on bone cells.

  19. Lipopolysaccharide induces autotaxin expression in human monocytic THP-1 cells

    International Nuclear Information System (INIS)

    Li Song; Zhang Junjie

    2009-01-01

    Autotaxin (ATX) is a secreted enzyme with lysophospholipase D (lysoPLD) activity, which converts lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a bioactive phospholipid involved in numerous biological activities, including cell proliferation, differentiation, and migration. In the present study, we found that bacterial lipopolysaccharide (LPS), a well-known initiator of the inflammatory response, induced ATX expression in monocytic THP-1 cells. The activation of PKR, JNK, and p38 MAPK was required for the ATX induction. The LPS-induced ATX in THP-1 cells was characterized as the β isoform. In the presence of LPC, ATX could promote the migrations of THP-1 and Jurkat cells, which was inhibited by pertussis toxin (PTX), an inhibitor of Gi-mediated LPA receptor signaling. In summary, LPS induces ATX expression in THP-1 cells via a PKR, JNK and p38 MAPK-mediated mechanism, and the ATX induction is likely to enhance immune cell migration in proinflammatory response by regulating LPA levels in the microenvironment.

  20. Benzoxazole derivatives suppress lipopolysaccharide-induced mast cell activation.

    Science.gov (United States)

    Cho, Kyung-Ah; Park, Minhwa; Kim, Yu-Hee; Choo, Hea-Young Park; Lee, Kyung Ho

    2018-05-01

    Mast cells are central regulators of allergic inflammation that function by releasing various proallergic inflammatory mediators, including histamine, eicosanoids and proinflammatory cytokines. Occasionally, bacterial infections may initiate or worsen allergic inflammation. A number of studies have indicated that activation of lipoxygenase in mast cells positive regulates allergic inflammatory responses by generating leukotrienes and proinflammatory cytokines. In the present study, the effects of benzoxazole derivatives on the lipopolysaccharide (LPS)‑induced expression of proinflammatory cytokines, production of histamine and surface expression of co‑stimulatory molecules on bone marrow-derived mast cells (BMMCs) were studied. The benzoxazole derivatives significantly reduced the expression of interleukin (IL)‑1β, IL‑6, IL‑13, tumor necrosis factor‑α, perilipin (PLIN) 2, and PLIN3 in BMMCs treated with LPS. Furthermore, histamine production was suppressed in BMMCs treated with LPS, or treated with phorbol-12-myristate-13-acetate/ionomycin. Benzoxazole derivatives marginally affected the surface expression of cluster of differentiation (CD)80 and CD86 on BMMCs in the presence of LPS, although LPS alone did not increase the expression of those proteins. Therefore, benzoxazole derivatives inhibited the secretion of proinflammatory cytokines in mast cells and may be potential candidate anti‑allergic agents to suppress mast cell activation.

  1. Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: 2010lijianguo@sina.cn [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

  2. Sulforaphane Inhibits Lipopolysaccharide-Induced Inflammation, Cytotoxicity, Oxidative Stress, and miR-155 Expression and Switches to Mox Phenotype through Activating Extracellular Signal-Regulated Kinase 1/2-Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway in Murine Microglial Cells.

    Science.gov (United States)

    Eren, Erden; Tufekci, Kemal Ugur; Isci, Kamer Burak; Tastan, Bora; Genc, Kursad; Genc, Sermin

    2018-01-01

    Sulforaphane (SFN) is a natural product with cytoprotective, anti-inflammatory, and antioxidant effects. In this study, we evaluated the mechanisms of its effects on lipopolysaccharide (LPS)-induced cell death, inflammation, oxidative stress, and polarization in murine microglia. We found that SFN protects N9 microglial cells upon LPS-induced cell death and suppresses LPS-induced levels of secreted pro-inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. SFN is also a potent inducer of redox sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), which is responsible for the transcription of antioxidant, cytoprotective, and anti-inflammatory genes. SFN induced translocation of Nrf2 to the nucleus via extracellular signal-regulated kinase 1/2 (ERK1/2) pathway activation. siRNA-mediated knockdown study showed that the effects of SFN on LPS-induced reactive oxygen species, reactive nitrogen species, and pro-inflammatory cytokine production and cell death are partly Nrf2 dependent. Mox phenotype is a novel microglial phenotype that has roles in oxidative stress responses. Our results suggested that SFN induced the Mox phenotype in murine microglia through Nrf2 pathway. SFN also alleviated LPS-induced expression of inflammatory microRNA, miR-155. Finally, SFN inhibits microglia-mediated neurotoxicity as demonstrated by conditioned medium and co-culture experiments. In conclusion, SFN exerts protective effects on microglia and modulates the microglial activation state.

  3. Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice

    Directory of Open Access Journals (Sweden)

    Jong Min Baek

    2014-08-01

    Full Text Available Aconitum pseudo-laeve var. erectum (APE has been widely shown in herbal medicine to have a therapeutic effect on inflammatory conditions. However, there has been no evidence on whether the extract of APE is involved in the biological bone metabolism process, particularly osteoclast-mediated bone resorption. In this study, we confirmed that the administration of APE could restore normal skeletal conditions in a murine model of lipopolysaccharide (LPS-induced bone loss via a decrease in the receptor activator of nuclear factor kappa-B ligand (RANKL/osteoprotegerin (OPG ratio and osteoclast number. We then investigated the effect of APE on the RANKL-induced formation and function of osteoclasts to elucidate its underlying molecular mechanisms. APE suppressed the formation of tartrate-resistant acid phosphatase (TRAP-positive cells, as well as the bone-resorbing activity of mature osteoclasts. Furthermore, APE attenuated nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1 and c-Fos without affecting any early signal pathway of osteoclastogenesis. Subsequently, APE significantly downregulated the expression of various genes exclusively expressed in osteoclasts. These results demonstrate that APE restores LPS-induced bone loss through a decrease of the serum RANKL/OPG ratio, and inhibits osteoclast differentiation and function, suggesting the promise of APE as a potential cure for various osteoclast-associated bone diseases.

  4. Dynamic Regulation of Delta-Opioid Receptor in Rat Trigeminal Ganglion Neurons by Lipopolysaccharide-induced Acute Pulpitis.

    Science.gov (United States)

    Huang, Jin; Lv, Yiheng; Fu, Yunjie; Ren, Lili; Wang, Pan; Liu, Baozhu; Huang, Keqiang; Bi, Jing

    2015-12-01

    Delta-opioid receptor (DOR) and its endogenous ligands distribute in trigeminal system and play a very important role in modulating peripheral inflammatory pain. DOR activation can trigger p44/42 mitogen-activated protein kinase (ERK1/2) and Akt signaling pathways, which participate in anti-inflammatory and neuroprotective effects. In this study, our purpose was to determine the dynamic changes of DOR in trigeminal ganglion (TG) neurons during the process of acute dental pulp inflammation and elucidate its possible mechanism. Forty rats were used to generate lipopolysaccharide-induced acute pulpitis animal models at 6, 12, and 24 hours and sham-operated groups. Acute pulpitis was confirmed by hematoxylin-eosin staining, and TG neuron activation was determined by anti-c-Fos immunohistochemistry. DOR protein and gene expression in TG was investigated by immunohistochemistry, Western blotting, and real-time polymerase chain reaction, and DOR expression in trigeminal nerves and dental pulp was also determined by immunohistochemistry. To further investigate the mechanism of DOR modulating acute inflammation, the change of pErk1/2 and pAkt in TG was examined by immunohistochemistry. Lipopolysaccharide could successfully induce acute pulpitis and activated TG neurons. Acute pulpitis could dynamically increase DOR protein and gene expression at 6, 12, and 24 hours in TG, and DOR dimerization was significantly increased at 12 and 24 hours. Acute pulpitis also induced the dynamic change of DOR protein in trigeminal nerve and dental pulp. Furthermore, ERK1/2 and Akt signaling pathways were inhibited in TG after acute pulpitis. Increased DOR expression and dimerization may play important roles in peripheral acute inflammatory pain. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. Reactive oxygen species are involved in lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation in mice.

    Science.gov (United States)

    Xu, De-Xiang; Chen, Yuan-Hua; Zhao, Lei; Wang, Hua; Wei, Wei

    2006-12-01

    Maternal infection is a cause of adverse developmental outcomes including embryonic resorption, intrauterine fetal death, and preterm labor. Lipopolysaccharide-induced developmental toxicity at early gestational stages has been well characterized. The purpose of the present study was to investigate the effects of maternal lipopolysaccharide exposure at late gestational stages on intrauterine fetal growth and skeletal development and to assess the potential role of reactive oxygen species in lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation. The timed pregnant CD-1 mice were intraperitoneally injected with lipopolysaccharide (25 to 75 microg/kg per day) on gestational day 15 to 17. To investigate the role of reactive oxygen species on lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation, the pregnant mice were injected with alpha-phenyl-N-t-butylnitrone (100 mg/kg, intraperitoneally) at 30 minutes before lipopolysaccharide (75 microg/kg per day, intraperitoneally), followed by an additional dose of alpha-phenyl-N-t-butylnitrone (50 mg/kg, intraperitoneally) at 3 hours after lipopolysaccharide. The number of live fetuses, dead fetuses, and resorption sites was counted on gestational day 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Maternal lipopolysaccharide exposure significantly increased fetal mortality, reduced fetal weight and crown-rump and tail lengths of live fetuses, and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges, and supraoccipital bone in a dose-dependent manner. Alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, almost completely blocked lipopolysaccharide-induced fetal death (63.2% in lipopolysaccharide group versus 6.5% in alpha-phenyl-N-t-butylnitrone + lipopolysaccharide group, P intrauterine growth restriction

  6. Glucocorticoid inhibition of leptin- and lipopolysaccharide-induced interleukin-6 production in obesity.

    Science.gov (United States)

    Huang, Chun-Jung; Acevedo, Edmund O; Mari, David C; Randazzo, Christopher; Shibata, Yoshimi

    2014-01-01

    Obesity is considered a chronic inflammatory condition that enhances the risk of numerous inflammatory diseases, including diabetes and cardiovascular disease. Glucocorticoids (GCs) and synthetic therapeutic GCs are anti-inflammatory agents, but the exact functions of GCs in obesity-related inflammation are unknown. Therefore, the objective of this study was to examine the inhibitory effect of an exogenous GC (dexamethasone, DEX) on leptin- and lipopolysaccharide (LPS)-induced IL-6 production by peripheral blood mononuclear cells (PBMCs) ex vivo in obese subjects compared to normal-weight subjects. Blood samples were drawn from 14 obese (BMI>30 kg/m(2)) and 14 normal-weight (BMIobese subjects showed greater leptin- and LPS-induced IL-6 production compared to normal-weight subjects. The suppressive effect of DEX on leptin- and LPS-induced IL-6 production (IC50) was not different between the two groups. However, the IC50 of DEX for LPS-induced was correlated with BMI, waist circumference, and hip circumference. These findings suggest that reduced GC sensitivity may be an important mechanism in the up-regulation of selected obese inflammation. Published by Elsevier Inc.

  7. Murine P-glycoprotein deficiency alters intestinal injury repair and blunts lipopolysaccharide-induced radioprotection.

    Science.gov (United States)

    Staley, Elizabeth M; Yarbrough, Vanisha R; Schoeb, Trenton R; Daft, Joseph G; Tanner, Scott M; Steverson, Dennis; Lorenz, Robin G

    2012-09-01

    P-glycoprotein (P-gp) has been reported to increase stem cell proliferation and regulate apoptosis. Absence of P-gp results in decreased repair of intestinal epithelial cells after chemical injury. To further explore the mechanisms involved in the effects of P-gp on intestinal injury and repair, we used the well-characterized radiation injury model. In this model, injury repair is mediated by production of prostaglandins (PGE(2)) and lipopolysaccharide (LPS) has been shown to confer radioprotection. B6.mdr1a(-/-) mice and wild-type controls were subjected to 12 Gy total body X-ray irradiation and surviving crypts in the proximal jejunum and distal colon were evaluated 3.5 days after irradiation. B6.mdr1a(-/-) mice exhibited normal baseline stem cell proliferation and COX dependent crypt regeneration after irradiation. However, radiation induced apoptosis was increased and LPS-induced radioprotection was blunted in the C57BL6.mdr1a(-/-) distal colon, compared to B6 wild-type controls. The LPS treatment induced gene expression of the radioprotective cytokine IL-1α, in B6 wild-type controls but not in B6.mdr1a(-/-) animals. Lipopolysaccharid-induced radioprotection was absent in IL-1R1(-/-) animals, indicating a role for IL-1α in radioprotection, and demonstrating that P-gp deficiency interferes with IL-1α gene expression in response to systemic exposure to LPS.

  8. Paeonol attenuates lipopolysaccharide-induced depressive-like behavior in mice.

    Science.gov (United States)

    Tao, Weiwei; Wang, Hanqing; Su, Qiang; Chen, Yanyan; Xue, Wenda; Xia, Baomei; Duan, Jinao; Chen, Gang

    2016-04-30

    The present study was designed to detect the anti-depressant effects of paeonol and the possible mechanisms in the lipopolysaccharide-induced depressive-like behavior. Open-field test(OFT), tail suspension test(TST) and forced swimming test(FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in mice hippocampus were determined by HPLC-ECD. Serum interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Our results showed that LPS significantly decreased the levels of 5-HT and NE in the hippocampus. LPS also reduced open-field activity, as well as increased immobility duration in FST and TST. Paeonol administration could effectively reverse the alterations in the concentrations of 5-HT, NE and reduce the IL-6 and TNF-α levels. Moreover, paeonol effectively downregulated brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB) and Nuclear factor-κB (NF-κB) in hippocampal. In conclusion, paeonol administration exhibited significant antidepressant-like effects in mice with LPS-induced depression. Copyright © 2016. Published by Elsevier Ireland Ltd.

  9. Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes

    Directory of Open Access Journals (Sweden)

    Hussain S

    2012-03-01

    were found either in vesicles or free in the cytoplasm. However, no significant differences in secreted cytokine profiles were observed between CeO2 nanoparticle-treated cells and control cells at noncytotoxic doses. No significant effects of CeO2 nanoparticle exposure subsequent to lipopolysaccharide priming was observed on cytokine secretion. Moreover, no significant difference in lipopolysaccharide-induced cytokine production was observed after exposure to CeO2 nanoparticles followed by lipopolysaccharide exposure.Conclusion: CeO2 nanoparticles at noncytotoxic concentrations neither modulate pre-existing inflammation nor prime for subsequent exposure to lipopolysaccharides in human monocytes from healthy subjects.Keywords: cerium dioxide, nanoparticle, nanomedicine, inflammation, human monocyte, lipopolysaccharides

  10. Inhibition of nuclear waste solutions containing multiple aggressive anions

    International Nuclear Information System (INIS)

    Congdon, J.W.

    1987-01-01

    The inhibition of localized corrosion of carbon steel in caustic, high-level radioactive waste solutions was studied using cyclic potentiodynamic polarization scans, supplemented by partially immersed coupon tests. The electrochemical tests provided a rapid and accurate means of determining the relationship between the minimum inhibitor requirements and the concentration of the aggressive anions in this system. Nitrate, sulfate, chloride, and fluoride were identified as aggressive anions, however, no synergistic effects were observed between these anions. This observation may have important theoretical implications because it tends to contradict the behavior of aggressive anions as predicted by existing theories for localized corrosion. 10 refs., 5 figs., 2 tabs

  11. Cytokine and acute phase protein gene expression in liver biopsies from dairy cows with a lipopolysaccharide - induced mastitis

    DEFF Research Database (Denmark)

    Vels, J; Røntved, Christine M.; Bjerring, Martin

    2009-01-01

    A minimally invasive liver biopsy technique was tested for its applicability to study the hepatic acute phase response (APR) in dairy cows with Escherichia coli lipopolysaccharide (LPS)-induced mastitis. The hepatic mRNA expression profiles of the inflammatory cytokines, tumor necrosis factor (TNF......, a minimally invasive liver biopsy technique can be used for studying the hepatic APR in diseased cattle. Lipopolysaccharide-induced mastitis resulted in a time-dependent production of inflammatory cytokines and SAA and Hp in the liver of dairy cows.......- ), IL-1β, IL-6, and IL-10, and the acute phase proteins serum amyloid A isoform 3 (SAA3), haptoglobin (Hp), and 1-acid glycoprotein (AGP) were determined by real-time reverse transcription-PCR. Fourteen primiparous cows in mid lactation were challenged with 200 µg of LPS (n = 8) or NaCl solution (n = 6...

  12. Acanthopanax trifoliatus inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Tzu-Mei Chien

    2015-10-01

    Full Text Available Acanthopanax trifoliatus is a well-known herb that is used for the treatment of bruising, neuralgia, impotence, and gout in Taiwan. This herb exhibits multifunctional activities, including anticancer, anti-inflammation, and antioxidant effects. This paper investigated the in vitro and in vivo anti-inflammatory effect of A. trifoliatus. High-performance liquid chromatography analysis established the fingerprint chromatogram of the ethyl acetate fraction of A. trifoliatus (EAAT. The anti-inflammatory effect of EAAT was detected using lipopolysaccharide (LPS stimulation of the mouse macrophage cell line RAW264.7 in vitro and LPS-induced lung injury in vivo. The effects of EAAT on LPS-induced production of inflammatory mediators in RAW264.7 murine macrophages and the mouse model were measured using enzyme-linked immunosorbent assay and Western blot. EAAT attenuated the production of LPS-induced nitric oxide (NO, tumor necrosis factor-alpha, interleukin-1β (IL-1β, and IL-6 in vitro and in vivo. Pretreatment with EAAT markedly reduced LPS-induced histological alterations in lung tissues. Furthermore, EAAT significantly reduced the number of total cells and protein concentration levels in the bronchoalveolar lavage fluid. Western blotting test results revealed that EAAT blocked protein expression of inducible NO synthase, cyclooxygenase-2, phosphorylation of Nuclear factor-kappa-B Inhibitor alpha (IκB-α protein, and mitogen-activated protein kinases in LPS-stimulated RAW264.7 cells as well as LPS-induced lung injury. This study suggests that A. trifoliatus may be a potential therapeutic candidate for the treatment of inflammatory diseases.

  13. AWRK6, A Synthetic Cationic Peptide Derived from Antimicrobial Peptide Dybowskin-2CDYa, Inhibits Lipopolysaccharide-Induced Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Qiuyu Wang

    2018-02-01

    Full Text Available Lipopolysaccharides (LPS are major outer membrane components of Gram-negative bacteria and produce strong inflammatory responses in animals. Most antibiotics have shown little clinical anti-endotoxin activity while some antimicrobial peptides have proved to be effective in blocking LPS. Here, the anti-LPS activity of the synthetic peptide AWRK6, which is derived from antimicrobial peptide dybowskin-2CDYa, has been investigated in vitro and in vivo. The positively charged α-helical AWRK6 was found to be effective in blocking the binding of LBP (LPS binding protein with LPS in vitro using ELISA. In a murine endotoxemia model, AWRK6 offered satisfactory protection efficiency against endotoxemia death, and the serum levels of LPS, IL-1β, IL-6, and TNF-α were found to be attenuated using ELISA. Further, histopathological analysis suggested that AWRK6 could improve the healing of liver and lung injury in endotoxemia mice. The results of real-time PCR and Western blotting showed that AWRK6 significantly reversed LPS-induced TLR4 overexpression and IκB depression, as well as the enhanced IκB phosphorylation. Additionally, AWRK6 did not produce any significant toxicity in vivo and in vitro. In summary, AWRK6 showed efficacious protection from LPS challenges in vivo and in vitro, by blocking LPS binding to LBP, without obvious toxicity, providing a promising strategy against LPS-induced inflammatory responses.

  14. BG-4, a novel bioactive peptide from Momordica charantia, inhibits lipopolysaccharide-induced inflammation in THP-1 human macrophages

    Science.gov (United States)

    Background: Bitter melon (Momordica charantia) is a commonly used food crop for management of a variety of diseases most notably for control of diabetes, a disease associated with aberrant inflammation. Purpose: To evaluate the anti-inflammatory property of BG-4, a novel bioactive peptide isolated f...

  15. Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures

    OpenAIRE

    Yan Zhu; Xiao Chen; Zhan Liu; Yu-Ping Peng; Yi-Hua Qiu

    2015-01-01

    Interleukin (IL)-10, an anti-inflammatory cytokine, is expressed in the brain and can inhibit microglial activation. Herein, we utilized lipopolysaccharide (LPS)-induced inflammatory Parkinson?s disease (PD) cell model to determine whether microglia and astrocytes are necessary targets for IL-10 neuroprotection. Primary ventral mesencephalic (VM) cultures with different composition of neurons, microglia and astrocytes were prepared. The cells were exposed to IL-10 (15, 50 or 150 ng/mL) 1 h pr...

  16. Resveratrol Protects Dopamine Neurons Against Lipopolysaccharide-Induced Neurotoxicity through Its Anti-Inflammatory Actions

    Science.gov (United States)

    Zhang, Feng; Shi, Jing-Shan; Zhou, Hui; Wilson, Belinda; Hong, Jau-Shyong

    2010-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by a progressive loss of dopamine (DA) neurons in the substantia nigra. Accumulating evidence indicates that inhibition of microglia-mediated neuroinflammation may become a reliable protective strategy for PD. Resveratrol, a nonflavonoid polyphenol naturally found in red wine and grapes, has been known to possess antioxidant, anticancer, and anti-inflammatory properties. Although recent studies have shown that resveratrol provided neuroprotective effects against ischemia, seizure, and neurodegenerative disorders, the mechanisms underlying its beneficial effects on dopaminergic neurodegeneration are poorly defined. In this study, rat primary midbrain neuron-glia cultures were used to elucidate the molecular mechanisms underlying resveratrol-mediated neuroprotection. The results clearly demonstrated that resveratrol protected DA neurons against lipopolysaccharide (LPS)-induced neurotoxicity in concentration- and time-dependent manners through the inhibition of microglial activation and the subsequent reduction of proinflammatory factor release. Mechanistically, resveratrol-mediated neuroprotection was attributed to the inhibition of NADPH oxidase. This conclusion is supported by the following observations. First, resveratrol reduced NADPH oxidase-mediated generation of reactive oxygen species. Second, LPS-induced translocation of NADPH oxidase cytosolic subunit p47 to the cell membrane was significantly attenuated by resveratrol. Third and most importantly, resveratrol failed to exhibit neuroprotection in cultures from NADPH oxidase-deficient mice. Furthermore, this neuroprotection was also related to an attenuation of the activation of mitogen-activated protein kinases and nuclear factor-κB signaling pathways in microglia. These findings suggest that resveratrol exerts neuroprotection against LPS-induced dopaminergic neurodegeneration, and NADPH oxidase may be a major player

  17. Effect of azithromycin on Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages.

    Science.gov (United States)

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-15

    Interleukin-6 (IL-6) is a key proinflammatory cytokine which plays a central role in the pathogenesis of periodontal disease. Host modulatory agents targeting at inhibiting IL-6, therefore, appear to be beneficial in slowing the progression of periodontal disease and potentially reducing destructive aspects of the host response. The present study was designed to investigate the effect of the macrolide antibiotic azithromycin on IL-6 generation in murine macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Azithromycin significantly suppressed IL-6 production as well as its mRNA expression in P. intermedia LPS-activated RAW264.7 cells. LPS-induced activation of JNK and p38 was not affected by azithromycin treatment. Azithromycin failed to prevent P. intermedia LPS from degrading IκB-α. Instead, azithromycin significantly diminished nuclear translocation and DNA binding activity of NF-κB p50 subunit induced with LPS. Azithromycin inhibited P. intermedia LPS-induced STAT1 and STAT3 phosphorylation. In addition, azithromycin up-regulated the mRNA level of SOCS1 in cells treated with LPS. In conclusion, azithromycin significantly attenuated P. intermedia LPS-induced production of IL-6 in murine macrophages via inhibition of NF-κB, STAT1 and STAT3 activation, which is possibly related to the activation of SOCS1 signaling. Further in vivo studies are required to better evaluate the potential of azithromycin in the treatment of periodontal disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Effects of propofol on lipopolysaccharide-induced expression and release of HMGB1 in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Wang, T.; Wei, X.Y.; Liu, B.; Wang, L.J.; Jiang, L.H. [Department of Anesthesiology, the Third Affiliated Hospital, Zhengzhou University, Zhengzhou (China)

    2015-02-24

    This study aimed to determine the effects of different concentrations of propofol (2,6-diisopropylphenol) on lipopolysaccharide (LPS)-induced expression and release of high-mobility group box 1 protein (HMGB1) in mouse macrophages. Mouse macrophage cell line RAW264.7 cells were randomly divided into 5 treatment groups. Expression levels of HMGB1 mRNA were detected using RT-PCR, and cell culture supernatant HMGB1 protein levels were detected using enzyme-linked immunosorbent assay (ELISA). Translocation of HMGB1 from the nucleus to the cytoplasm in macrophages was observed by Western blotting and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus was detected using ELISA. HMGB1 mRNA expression levels increased significantly in the cell culture supernatant and in cells after 24 h of stimulating RAW264.7 cells with LPS (500 ng/mL). However, HMGB1 mRNA expression levels in the P2 and P3 groups, which received 500 ng/mL LPS with 25 or 50 μmol/mL propofol, respectively, were significantly lower than those in the group receiving LPS stimulation (P<0.05). After stimulation by LPS, HMGB1 protein levels were reduced significantly in the nucleus but were increased in the cytoplasm (P<0.05). Simultaneously, the activity of NF-κB was enhanced significantly (P<0.05). After propofol intervention, HMGB1 translocation from the nucleus to the cytoplasm and NF-κB activity were inhibited significantly (each P<0.05). Thus, propofol can inhibit the LPS-induced expression and release of HMGB1 by inhibiting HMGB1 translocation and NF-κB activity in RAW264.7 cells, suggesting propofol may be protective in patients with sepsis.

  19. Atorvastatin reduces lipopolysaccharide-induced expression of cyclooxygenase-2 in human pulmonary epithelial cells

    Directory of Open Access Journals (Sweden)

    Chen Ping

    2005-04-01

    Full Text Available Abstract Objective To explore the effects of atorvastatin on expression of cyclooxygenase-2 (COX-2 in human pulmonary epithelial cells (A549. Methods A549 cells were incubated in DMEM medium containing lipopolysaccharide (LPS in the presence or absence of atorvastatin. After incubation, the medium was collected and the amount of prostaglandin E2 (PGE2 was measured by enzyme-linked immunosorbent assay (ELISA. The cells were harvested, and COX-2 mRNA and protein were analyzed by RT-PCR and western-blot respectively. Results LPS increased the expression of COX-2 mRNA and production of PGE2 in a dose- and time-dependent manner in A549. Induction of COX-2 mRNA and protein by LPS were inhibited by atorvastatin in a dose-dependent manner. Atorvastatin also significantly decreased LPS-induced production of PGE2. There was a positive correlation between reduced of COX-2 mRNA and decreased of PGE2 (r = 0.947, P Conclusion Atorvastatin down-regulates LPS-induced expression of the COX-2 and consequently inhibits production of PGE2 in cultured A549 cells.

  20. Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures

    Directory of Open Access Journals (Sweden)

    Yan Zhu

    2015-12-01

    Full Text Available Interleukin (IL-10, an anti-inflammatory cytokine, is expressed in the brain and can inhibit microglial activation. Herein, we utilized lipopolysaccharide (LPS-induced inflammatory Parkinson’s disease (PD cell model to determine whether microglia and astrocytes are necessary targets for IL-10 neuroprotection. Primary ventral mesencephalic (VM cultures with different composition of neurons, microglia and astrocytes were prepared. The cells were exposed to IL-10 (15, 50 or 150 ng/mL 1 h prior to LPS (50 ng/mL treatment. LPS induced dopaminergic and non-dopaminergic neuronal loss in VM cultures, VM neuron-enriched cultures, and neuron-microglia co-cultures, but not in neuron-astrocyte co-cultures. IL-10 reduced LPS-induced neuronal loss particularly in single VM neuron cultures. Pro-inflammatory mediators (TNF-α, IL-1β, inducible nitric oxide synthase and cyclooxygenase-2 were upregulated in both neuron-microglia and neuron-astrocyte co-cultures by LPS. In contrast, neurotrophic factors (brain-derived neurotrophic factor, insulin-like growth factor-1 or glial cell-derived neurotrophic factor were downregulated in neuron-microglia co-cultures, but upregulated in neuron-astrocyte co-cultures by LPS. IL-10 reduced both the increase in production of the pro-inflammatory mediators and the decrease in production of the neurotrophic factors induced by LPS. These results suggest that astrocytes can balance LPS neurotoxicity by releasing more neurotrophic factors and that IL-10 exerts neuroprotective property by an extensive action including direct on neurons and indirect via inhibiting microglial activation.

  1. Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures.

    Science.gov (United States)

    Zhu, Yan; Chen, Xiao; Liu, Zhan; Peng, Yu-Ping; Qiu, Yi-Hua

    2015-12-28

    Interleukin (IL)-10, an anti-inflammatory cytokine, is expressed in the brain and can inhibit microglial activation. Herein, we utilized lipopolysaccharide (LPS)-induced inflammatory Parkinson's disease (PD) cell model to determine whether microglia and astrocytes are necessary targets for IL-10 neuroprotection. Primary ventral mesencephalic (VM) cultures with different composition of neurons, microglia and astrocytes were prepared. The cells were exposed to IL-10 (15, 50 or 150 ng/mL) 1 h prior to LPS (50 ng/mL) treatment. LPS induced dopaminergic and non-dopaminergic neuronal loss in VM cultures, VM neuron-enriched cultures, and neuron-microglia co-cultures, but not in neuron-astrocyte co-cultures. IL-10 reduced LPS-induced neuronal loss particularly in single VM neuron cultures. Pro-inflammatory mediators (TNF-α, IL-1β, inducible nitric oxide synthase and cyclooxygenase-2) were upregulated in both neuron-microglia and neuron-astrocyte co-cultures by LPS. In contrast, neurotrophic factors (brain-derived neurotrophic factor, insulin-like growth factor-1 or glial cell-derived neurotrophic factor) were downregulated in neuron-microglia co-cultures, but upregulated in neuron-astrocyte co-cultures by LPS. IL-10 reduced both the increase in production of the pro-inflammatory mediators and the decrease in production of the neurotrophic factors induced by LPS. These results suggest that astrocytes can balance LPS neurotoxicity by releasing more neurotrophic factors and that IL-10 exerts neuroprotective property by an extensive action including direct on neurons and indirect via inhibiting microglial activation.

  2. DHA suppresses Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    Science.gov (United States)

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-14

    Several reports have indicated that dietary intake of DHA is associated with lower prevalence of periodontitis. In the present study, we investigated the effect of DHA on the production of proinflammatory mediators in murine macrophage-like RAW264.7 cells stimulated with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. LPS was isolated from lyophilised P. intermedia ATCC 25,611 cells using the standard hot-phenol-water protocol. Culture supernatants were collected and assayed for NO, IL-1β and IL-6. Real-time PCR analysis was carried out to detect the expression of inducible NO synthase (iNOS), IL-1β, IL-6 and haeme oxygenase-1 (HO-1) mRNA. Immunoblot analysis was carried out to quantify the expression of iNOS and HO-1 protein and concentrations of signalling proteins. DNA-binding activities of NF-κB subunits were determined using an ELISA-based assay kit. DHA significantly attenuated the production of NO, IL-1β and IL-6 at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. DHA induced the expression of HO-1 in cells treated with P. intermedia LPS. Selective inhibition of HO-1 activity by tin protoporphyrin IX significantly mitigated the inhibitory effects of DHA on LPS-induced NO production. DHA significantly attenuated the phosphorylation of c-Jun N-terminal kinase induced by LPS. In addition, DHA suppressed the transcriptional activity of NF-κB by regulating the nuclear translocation and DNA-binding activity of NF-κB p50 subunit and inhibited the phosphorylation of signal transducer and activator of transcription 1. Further in vivo studies are needed to better evaluate the potential of DHA in humans as a therapeutic agent to treat periodontal disease.

  3. Acrolein inhalation suppresses lipopolysaccharide-induced inflammatory cytokine production but does not affect acute airways neutrophilia.

    Science.gov (United States)

    Kasahara, David Itiro; Poynter, Matthew E; Othman, Ziryan; Hemenway, David; van der Vliet, Albert

    2008-07-01

    Acrolein is a reactive unsaturated aldehyde that is produced during endogenous oxidative processes and is a major bioactive component of environmental pollutants such as cigarette smoke. Because in vitro studies demonstrate that acrolein can inhibit neutrophil apoptosis, we evaluated the effects of in vivo acrolein exposure on acute lung inflammation induced by LPS. Male C57BL/6J mice received 300 microg/kg intratracheal LPS and were exposed to acrolein (5 parts per million, 6 h/day), either before or after LPS challenge. Exposure to acrolein either before or after LPS challenge did not significantly affect the overall extent of LPS-induced lung inflammation, or the duration of the inflammatory response, as observed from recovered lung lavage leukocytes and histology. However, exposure to acrolein after LPS instillation markedly diminished the LPS-induced production of several inflammatory cytokines, specifically TNF-alpha, IL-12, and the Th1 cytokine IFN-gamma, which was associated with reduction in NF-kappaB activation. Our data demonstrate that acrolein exposure suppresses LPS-induced Th1 cytokine responses without affecting acute neutrophilia. Disruption of cytokine signaling by acrolein may represent a mechanism by which smoking contributes to chronic disease in chronic obstructive pulmonary disease and asthma.

  4. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    International Nuclear Information System (INIS)

    Yoo, Seong Ho; Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2013-01-01

    Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI

  5. Pseudomonas aeruginosa lipopolysaccharide induces CF-like alteration of protein secretion by human tracheal gland cells.

    Science.gov (United States)

    Kammouni, W; Figarella, C; Baeza, N; Marchand, S; Merten, M D

    1997-12-18

    Human tracheal gland (HTG) serous cells are now believed to play a major role in the physiopathology of cystic fibrosis. Because of the persistent inflammation and the specific infection by Pseudomonas aeruginosa in the lung, we looked for the action of the lipopolysaccharide (LPS) of this bacteria on human tracheal gland cells in culture by studying the secretion of the secretory leukocyte proteinase inhibitor (SLPI) which is a specific serous secretory marker of these cells. Treatment with Pseudomonas aeruginosa LPS resulted in a significant dose-dependent increase in the basal production of SLPI (+ 250 +/- 25%) whilst the SLPI transcript mRNA levels remained unchanged. This LPS-induced increase in secretion was inhibited by glucocorticoides. Furthermore, LPS treatment of HTG cells induces a loss of responsiveness to carbachol and isoproterenol but not to adenosine triphosphate. These findings indicate that HTG cells treated by Pseudomonas aeruginosa LPS have the same behavior as those previously observed with CF-HTG cells. Exploration by using reverse transcriptase polymerase chain reaction amplification showed that LPS downregulated cystic fibrosis transmembrane conductance regulator (CFTR) mRNA expression in HTG cells indicative of a link between CFTR function and consequent CF-like alteration in protein secretory process.

  6. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Seong Ho, E-mail: yoosh@snu.ac.kr [Seoul National University Hospital, Biomedical Research Institute and Institute of Forensic Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Abdelmegeed, Mohamed A. [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States); Song, Byoung-Joon, E-mail: bj.song@nih.gov [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)

    2013-07-05

    Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI.

  7. A Fermented Whole Grain Prevents Lipopolysaccharides-Induced Dysfunction in Human Endothelial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Laura Giusti

    2017-01-01

    Full Text Available Endogenous and exogenous signals derived by the gut microbiota such as lipopolysaccharides (LPS orchestrate inflammatory responses contributing to development of the endothelial dysfunction associated with atherosclerosis in obesity, metabolic syndrome, and diabetes. Endothelial progenitor cells (EPCs, bone marrow derived stem cells, promote recovery of damaged endothelium playing a pivotal role in cardiovascular repair. Since healthy nutrition improves EPCs functions, we evaluated the effect of a fermented grain, Lisosan G (LG, on early EPCs exposed to LPS. The potential protective effect of LG against LPS-induced alterations was evaluated as cell viability, adhesiveness, ROS production, gene expression, and NF-kB signaling pathway activation. Our results showed that LPS treatment did not affect EPCs viability and adhesiveness but induced endothelial alterations via activation of NF-kB signaling. LG protects EPCs from inflammation as well as from LPS-induced oxidative and endoplasmic reticulum (ER stress reducing ROS levels, downregulating proinflammatory and proapoptotic factors, and strengthening antioxidant defense. Moreover, LG pretreatment prevented NF-kB translocation from the cytoplasm into the nucleus caused by LPS exposure. In human EPCs, LPS increases ROS and upregulates proinflammatory tone, proapoptotic factors, and antioxidants. LG protects EPCs exposed to LPS reducing ROS, downregulating proinflammatory and proapoptotic factors, and strengthening antioxidant defenses possibly by inhibiting NF-κB nuclear translocation.

  8. Fatty Acid Oxidation Compensates for Lipopolysaccharide-Induced Warburg Effect in Glucose-Deprived Monocytes

    Directory of Open Access Journals (Sweden)

    Nora Raulien

    2017-05-01

    Full Text Available Monocytes enter sites of microbial or sterile inflammation as the first line of defense of the immune system and initiate pro-inflammatory effector mechanisms. We show that activation with bacterial lipopolysaccharide (LPS induces them to undergo a metabolic shift toward aerobic glycolysis, similar to the Warburg effect observed in cancer cells. At sites of inflammation, however, glucose concentrations are often drastically decreased, which prompted us to study monocyte function under conditions of glucose deprivation and abrogated Warburg effect. Experiments using the Seahorse Extracellular Flux Analyzer revealed that limited glucose supply shifts monocyte metabolism toward oxidative phosphorylation, fueled largely by fatty acid oxidation at the expense of lipid droplets. While this metabolic state appears to provide sufficient energy to sustain functional properties like cytokine secretion, migration, and phagocytosis, it cannot prevent a rise in the AMP/ATP ratio and a decreased respiratory burst. The molecular trigger mediating the metabolic shift and the functional consequences is activation of AMP-activated protein kinase (AMPK. Taken together, our results indicate that monocytes are sufficiently metabolically flexible to perform pro-inflammatory functions at sites of inflammation despite glucose deprivation and inhibition of the LPS-induced Warburg effect. AMPK seems to play a pivotal role in orchestrating these processes during glucose deprivation in monocytes.

  9. Protective effects of kaempferol on lipopolysaccharide-induced mastitis in mice.

    Science.gov (United States)

    Cao, Rongfeng; Fu, Kaiqiang; Lv, Xiaopei; Li, Weishi; Zhang, Naisheng

    2014-10-01

    Kaempferol isolated from the root of Zingiberaceae plants galangal and other Chinese herbal medicines have been reported to have anti-inflammatory properties. However, the anti-inflammatory effects of kaempferol on lipopolysaccharide (LPS)-induced mastitis are unknown and their underlying molecular mechanisms remain to be explored. The aim of this study was to evaluate the effects of kaempferol on LPS-induced mouse mastitis. The mouse model of mastitis was induced by injection of LPS through the duct of mammary gland. Kaempferol was injected 1 h before and 12 h after induction of LPS intraperitoneally. The present results showed that kaempferol markedly reduced infiltration of neutrophilic granulocyte, activation of myeloperoxidase (MPO), expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in a dose-dependent manner, which were increased in LPS-induced mouse mastitis. Furthermore, kaempferol suppressed the phosphorylation of nuclear factor-κB (NF-κB) p65 subunit and the degradation of its inhibitor IκBα. All results suggest that anti-inflammatory effects of kaempferol against the LPS-induced mastitis possibly through inhibition of the NF-κB signaling pathway. Kaempferol may be a potential therapeutic agent for mastitis.

  10. Possible Mechanisms Involved in Attenuation of Lipopolysaccharide-Induced Memory Deficits by Methyl Jasmonate in Mice.

    Science.gov (United States)

    Eduviere, Anthony Taghogho; Umukoro, Solomon; Adeoluwa, Olusegun A; Omogbiya, Itivere Adrian; Aluko, Oritoke Modupe

    2016-12-01

    This present study was carried out to investigate the likely mechanisms by which methyl jasmonate (MJ), 'an agent widely used in aromatherapy for neurological disorders, attenuates lipopolysaccharide (LPS)-induced memory deficits in mice. Mice were given intraperitoneal administration of LPS (250 µg/kg) alone or in combination with MJ (10-40 mg/kg), donepezil, DP (1 mg/kg), or vehicle for 7 successive days. Thereafter, memory was assessed using object recognition test (ORT). Acetylcholinesterase and myeloperoxidase activities were estimated in brain tissue homogenates. Brain levels of nitric oxide and markers of oxidative stress as well as histopathologic changes of the prefrontal cortex and cornu ammonis 1 (CA1) of the hippocampal region were also assessed. MJ (10-40 mg/kg) attenuated LPS-induced memory impairment in ORT. Moreover, the increased brain activities of acetylcholinesterase and myeloperoxidase enzymes were suppressed by MJ when compared with control (p memory deficits via mechanisms related to inhibition of acetylcholinesterase, myeloperoxidase, oxidative stress and neuronal degeneration.

  11. Cardiac-specific overexpression of catalase attenuates lipopolysaccharide-induced myocardial contractile dysfunction: role of autophagy.

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F; Roe, Nathan D; Hu, Nan; Gao, Feng; Ren, Jun

    2012-09-15

    Lipopolysaccharide (LPS) from gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complications in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis, and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity, and carbonyl formation. A Kaplan-Meier curve was constructed for survival after LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice after LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O(2)(-), and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury after LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by the antioxidant N-acetylcysteine and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    Science.gov (United States)

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged with LPS (6 mg/kg) and cardiac function was evaluated. Levels of oxidative stress, autophagy, apoptosis and protein damage were examined using fluorescence microscopy, Western blot, TUNEL assay, caspase-3 activity and carbonyl formation. Kaplan-Meier curve was constructed for survival following LPS treatment. Our results revealed a lower mortality in catalase mice compared with FVB mice following LPS challenge. LPS injection led to depressed cardiac contractile capacity as evidenced by echocardiography and cardiomyocyte contractile function, the effect of which was ablated by catalase overexpression. LPS treatment induced elevated TNF-α level, autophagy, apoptosis (TUNEL, caspase-3 activation, cleaved caspase-3), production of ROS and O2−, and protein carbonyl formation, the effects of which were significantly attenuated by catalase overexpression. Electron microscopy revealed focal myocardial damage characterized by mitochondrial injury following LPS treatment, which was less severe in catalase mice. Interestingly, LPS-induced cardiomyocyte contractile dysfunction was prevented by antioxidant NAC and the autophagy inhibitor 3-methyladenine. Taken together, our data revealed that catalase protects against LPS-induced cardiac dysfunction and mortality, which may be associated with inhibition of oxidative stress and autophagy. PMID:22902401

  13. The effects of a novel botanical agent on lipopolysaccharide-induced alveolar bone loss in rats.

    Science.gov (United States)

    Lee, Bo-Ah; Lee, Hwa-Sun; Jung, Young-Suk; Kim, Se-Won; Lee, Yong-Wook; Chang, Sun-Hwa; Chung, Hyun-Ju; Kim, Ok-Su; Kim, Young-Joon

    2013-08-01

    The development of host-modulatory agents with low risk of adverse effects has been needed to treat periodontitis, a chronic inflammatory disease. A botanical mixture of extracts from two natural substances, Panax notoginseng and Rehmannia glutinosa Libosch, was developed as a novel botanical agent synthesized with anti-inflammatory effect. The aim of this study is to evaluate the effects of the botanical mixture on the release of inflammatory cytokines and its inhibitory effect on lipopolysaccharide (LPS)-induced alveolar bone loss (ABL) in a rat model. Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2yl)-5(3-carboxymethoxyphenol)-2-(4-sulfophenyl)-2H-tetrazolium assay using human gingival fibroblast (hGF) and human periodontal ligament (hPDL) cells. Human acute monocytic leukemia cell line and hGF cells were cultured to assay tumor necrosis factor (TNF)-α and interleukin (IL)-6, respectively. Microcomputed tomography analysis and immunofluoresence analysis were performed to evaluate the efficacy of the botanical mixture to inhibit the destruction of alveolar bone and connective tissue in a rat model. The botanical mixture is cytotoxic at concentrations exceeding 2.5 mg/mL (P botanical mixture to be used in all subsequent in vitro and in vivo experiments. The botanical mixture reduced the release of TNF-α and IL-6 from human monocytic cells and hGF cells in a dose-dependent manner (P botanical mixture significantly reduced the alveolar bone loss in a rat model (P botanical mixture, matrix metalloproteinase (MMP)-9 was detected along the alveolar bone crest (ABC), but not around the gingival connective tissue, while in the group with LPS-induced ABL, pronounced expression of MMP-9 around the ABC, periodontal ligament, and gingival connective tissue was found. The botanical mixture showed a potential adjunctive effect in the treatment of periodontitis. However, the present findings are obtained in vitro and in a rat model, so further clinical study is needed

  14. Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

    Science.gov (United States)

    Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

    2017-11-01

    Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the

  15. Beneficial effect of honokiol on lipopolysaccharide induced anxiety-like behavior and liver damage in mice.

    Science.gov (United States)

    Sulakhiya, Kunjbihari; Kumar, Parveen; Gurjar, Satendra S; Barua, Chandana C; Hazarika, Naba K

    2015-02-26

    Anxiety disorders are commonly occurring co-morbid neuropsychiatric disorders with chronic inflammatory conditions such as live damage. Numerous studies revealed that peripheral inflammation, oxidative stress and brain derived neurotrophic factor (BDNF) play important roles in the pathophysiology of anxiety disorders. Honokiol (HNK) is a polyphenol, possessing multiple biological activities including antioxidant, anti-inflammatory, anxiolytic, antidepressant and hepatoprotection. The present study was designed to investigate the effect of HNK, in lipopolysaccharide (LPS)-induced anxiety-like behavior and liver damage in mice. Mice (n=6-10/group) were pre-treated with different doses of HNK (2.5 and 5mg/kg; i.p.) for two days, and challenged with saline or LPS (0.83mg/kg; i.p.) on third day. Anxiety-like behavior was monitored using elevated plus maze (EPM) and open field test (OFT). Animals were sacrificed to evaluate various biochemical parameters in plasma and liver. HNK pre-treatment provided significant (P<0.01) protection against LPS-induced reduction in body weight, food and water intake in mice. HNK at higher dose significantly (P<0.05) attenuated LPS-induced anxiety-like behavior by increasing the number of entries and time spent in open arm in EPM test, and by increasing the frequency in central zone in OFT. HNK pre-treatment ameliorated LPS-induced peripheral inflammation by reducing plasma IL-1β, IL-6, TNF-α level, and also improved the plasma BDNF level, prevented liver damage via attenuating transaminases (AST, ALT), liver oxidative stress and TNF-α activity in LPS challenged mice. In conclusion, the current investigation suggests that HNK provided beneficial effect against LPS-induced anxiety-like behavior and liver damage which may be governed by inhibition of cytokines production, oxidative stress and depletion of plasma BDNF level. Our result suggests that HNK could be a therapeutic approach for the treatment of anxiety and other

  16. Inhibiting pitting corrosion in carbon steel exposed to dilute radioactive waste slurries

    International Nuclear Information System (INIS)

    Zapp, P.E.; Hobbs, D.T.

    1991-01-01

    Dilute caustic high-level radioactive waste slurries can induce pitting corrosion in carbon steel. Cyclic potentiodynamic polarization tests were conducted in simulated and actual waste solutions to determine minimum concentrations of sodium nitrate which inhibit pitting in ASTM A537 class 1 steel exposed to these solutions. Susceptibility to pitting was assessed through microscopic inspection of specimens and inspection of polarization scans. Long-term coupon immersion tests were conducted to verify the nitrite concentrations established by the cyclic potentiodynamic polarization tests. The minimum effective nitrite concentration is expressed as a function of the waste nitrate concentration and temperature

  17. Evaluating inhibition conditions in high-solids anaerobic digestion of organic fraction of municipal solid waste.

    Science.gov (United States)

    Schievano, Andrea; D'Imporzano, Giuliana; Malagutti, Luca; Fragali, Emilio; Ruboni, Gabriella; Adani, Fabrizio

    2010-07-01

    High-solids anaerobic digestion (HSAD) processes, when applied to different types of organic fractions of municipal solid waste (OFMSW), may easily be subjected to inhibition due to organic overloading. In this study, a new approach for predicting these phenomena was proposed based on the estimation of the putrescibility (oxygen consumption in 20 h biodegradation, OD(20)) of the organic mixtures undergoing the HSAD process. Different wastes exhibiting different putrescibility were subjected to lab-scale batch-HSAD. Measuring the organic loading (OL) as volatile solids (VS) was found unsuitable for predicting overload inhibition, because similar VS contents corresponded to both inhibited and successful trials. Instead, the OL calculated as OD(20) was a very good indicator of the inhibiting conditions (inhibition started for OD(20)>17-18 g O(2)kg(-1)). This new method of predicting inhibition in the HSAD process of diverse OFMSW may be useful for developing a correct approach to the technology in very different contexts. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  18. [Inhibition of chlorobenzene formation via various routes during waste incineration by ammonium sulfate and urea].

    Science.gov (United States)

    Yan, Mi; Qi, Zhi-Fu; Li, Xiao-Dong; Hu, Yan-Jun; Chen, Tong

    2014-01-01

    Chlorobenzene (CBz) is the precursor of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/Fs) generated in the processes of waste incineration, and it is regarded as a good indicator of PCDD/Fs for realizing PCDD/Fs online monitoring, moreover, pentachlorobenzene (PeCBz) and Hexachlorobenzene (HxCBz) belong to Persistent Organic Pollutants (POPs). However, the emission control of CBz in waste incineration does not attract enough attention, so this study focused on the inhibition of the 3 CBz formation routes in waste combustion by ammonium sulfate and urea, including CB formation from fly ash, CB formation from 1,2-dichlorobenzene (1,2-DiCBz) and the combustion of model medical waste. The results showed that both ammonium sulfate and urea reduced CBz yield during these three thermal processes. For instance, the inhibition rates of tetrachlorobenzene (TeCBz), PeCBz and HxCBz were 66.8%, 57.4% and 50.4%, respectively, when 1% urea was co-combusted with medical waste. By comparing the effect of ammonium sulfate and urea on CBz formation by three routes, urea was considered as a comparatively stable inhibitor for CBz.

  19. Selumetinib Attenuates Skeletal Muscle Wasting in Murine Cachexia Model through ERK Inhibition and AKT Activation.

    Science.gov (United States)

    Quan-Jun, Yang; Yan, Huo; Yong-Long, Han; Li-Li, Wan; Jie, Li; Jin-Lu, Huang; Jin, Lu; Peng-Guo, Chen; Run, Gan; Cheng, Guo

    2017-02-01

    Cancer cachexia is a multifactorial syndrome affecting the skeletal muscle. Previous clinical trials showed that treatment with MEK inhibitor selumetinib resulted in skeletal muscle anabolism. However, it is conflicting that MAPK/ERK pathway controls the mass of the skeletal muscle. The current study investigated the therapeutic effect and mechanisms of selumetinib in amelioration of cancer cachexia. The classical cancer cachexia model was established via transplantation of CT26 colon adenocarcinoma cells into BALB/c mice. The effect of selumetinib on body weight, tumor growth, skeletal muscle, food intake, serum proinflammatory cytokines, E3 ligases, and MEK/ERK-related pathways was analyzed. Two independent experiments showed that 30 mg/kg/d selumetinib prevented the loss of body weight in murine cachexia mice. Muscle wasting was attenuated and the expression of E3 ligases, MuRF1 and Fbx32, was inhibited following selumetinib treatment of the gastrocnemius muscle. Furthermore, selumetinib efficiently reduced tumor burden without influencing the cancer cell proliferation, cumulative food intake, and serum cytokines. These results indicated that the role of selumetinib in attenuating muscle wasting was independent of cancer burden. Detailed analysis of the mechanism revealed AKT and mTOR were activated, while ERK, FoxO3a, and GSK3β were inhibited in the selumetinib -treated cachexia group. These indicated that selumetinib effectively prevented skeletal muscle wasting in cancer cachexia model through ERK inhibition and AKT activation in gastrocnemius muscle via cross-inhibition. The study not only elucidated the mechanism of MEK/ERK inhibition in skeletal muscle anabolism, but also validated selumetinib therapy as an effective intervention against cancer cachexia. Mol Cancer Ther; 16(2); 334-43. ©2016 AACR. ©2016 American Association for Cancer Research.

  20. The Role of Interleukin-6 in Lipopolysaccharide-Induced Weight Loss, Hypoglycemia and Fibrinogen Production, in Vivo

    Science.gov (United States)

    1994-07-01

    result in chronic wasting or cachexia. In neoplastic severe weight loss in syngeneic hosts.6 In this model, diseases, the presence of wasting of muscle...48 h post-endotoxin). Anti-TNF MAb tribution of TNF and IL-6 in several metabolic changes reduced by c. 50% the LPS-induced weight loss, but...similar results. Also, the addi- hypertriglyceridemia , hypoglycemia as well as stimu- tion of fresh 20F3 MAb to diluted serum sample from late the

  1. Long chain fatty acids (LCFA) evolution for inhibition forecasting during anaerobic treatment of lipid-rich wastes: Case of milk-fed veal slaughterhouse waste.

    Science.gov (United States)

    Rodríguez-Méndez, R; Le Bihan, Y; Béline, F; Lessard, P

    2017-09-01

    A detailed study of a solid slaughterhouse waste (SHW) anaerobic treatment is presented. The waste used in this study is rich in lipids and proteins residue. Long chain fatty acids (LCFA), coming from the hydrolysis of lipids were inhibitory to anaerobic processes at different degrees. Acetogenesis and methanogenesis processes were mainly affected by inhibition whereas disintegration and hydrolysis processes did not seem to be affected by high LCFA concentrations. Nevertheless, because of the high energy content, this kind of waste is very suitable for anaerobic digestion but strict control of operating conditions is required to prevent inhibition. For that, two inhibition indicators were identified in this study. Those two indicators, LCFA dynamics and LCFA/VS biomass ratio proved to be useful to predict and to estimate the process inhibition degree. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells

    International Nuclear Information System (INIS)

    Patel, Devang N.; Bailey, Steven R.; Gresham, John K.; Schuchman, David B.; Shelhamer, James H.; Goldstein, Barry J.; Foxwell, Brian M.; Stemerman, Michael B.; Maranchie, Jodi K.; Valente, Anthony J.; Mummidi, Srinivas; Chandrasekar, Bysani

    2006-01-01

    CXCL16 is a transmembrane non-ELR CXC chemokine that signals via CXCR6 to induce aortic smooth muscle cell (ASMC) proliferation. While bacterial lipopolysaccharide (LPS) has been shown to stimulate CXCL16 expression in SMC, its effects on CXCR6 are not known. Here, we demonstrate that LPS upregulates CXCR6 mRNA, protein, and surface expression in human ASMC. Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS-mediated CXCR6 expression. LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-κB (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression. Using dominant negative expression vectors and siRNA interference, we demonstrate that LPS induces AP-1 activation via MyD88, TRAF6, ERK1/2, and JNK signaling pathways. Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS-mediated AP-1-dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA. Finally, CXCR6 knockdown inhibited CXCL16-induced ASMC proliferation. These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis

  3. Mitochondrial reactive oxygen species mediate the lipopolysaccharide-induced pro-inflammatory response in human gingival fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xue; Wang, Xiaoxuan [Department of Periodontology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China); Zheng, Ming, E-mail: zhengm@bjmu.edu.cn [Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191 (China); Luan, Qing Xian, E-mail: kqluanqx@126.com [Department of Periodontology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081 (China)

    2016-09-10

    Although periodontal diseases are initiated by bacteria that colonize the tooth surface and gingival sulcus, the host response is believed to play an essential role in the breakdown of connective tissue and bone. Mitochondrial reactive oxygen species (mtROS) have been proposed to regulate the activation of the inflammatory response by the innate immune system. However, the role of mtROS in modulating the response of human gingival fibroblasts (HGFs) to immune stimulation by lipopolysaccharides (LPS) has yet to be fully elucidated. Here, we showed that LPS from Porphyromonas gingivalis stimulated HGFs to increase mtROS production, which could be inhibited by treatment with a mitochondrial-targeted exogenous antioxidant (mito-TEMPO) or transfection with manganese superoxide dismutase (MnSOD). A time-course study revealed that an increase in the concentration of mtROS preceded the expression of inflammatory cytokines in HGFs. Mito-TEMPO treatment or MnSOD transfection also significantly prevented the LPS-induced increase of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Furthermore, suppressing LPS-induced mtROS generation inhibited the activation of p38, c-Jun N-terminal kinase, and inhibitor of nuclear factor-κB kinase, as well as the nuclear localization of nuclear factor-κB. These results demonstrate that mtROS generation is a key signaling event in the LPS-induced pro-inflammatory response of HGFs. - Highlights: • Inflammation is thought to promote pathogenic changes in periodontitis. • We investigated mtROS as a regulator of inflammation in gingival fibroblasts. • Targeted antioxidants were used to inhibit mtROS production after LPS challenge. • Inhibiting mtROS generation suppressed the secretion of pro-inflammatory cytokines. • JNK, p38, IKK, and NF-κB were shown to act as transducers of mtROS signaling.

  4. Acrolein Inhalation Suppresses Lipopolysaccharide-Induced Inflammatory Cytokine Production but Does Not Affect Acute Airways Neutrophilia1

    OpenAIRE

    Kasahara, David Itiro; Poynter, Matthew E.; Othman, Ziryan; Hemenway, David; van der Vliet, Albert

    2008-01-01

    Acrolein is a reactive unsaturated aldehyde that is produced during endogenous oxidative processes and is a major bioactive component of environmental pollutants such as cigarette smoke. Because in vitro studies demonstrate that acrolein can inhibit neutrophil apoptosis, we evaluated the effects of in vivo acrolein exposure on acute lung inflammation induced by LPS. Male C57BL/6J mice received 300 μg/kg intratracheal LPS and were exposed to acrolein (5 parts per million, 6 h/day), either befo...

  5. Mitochondrial reactive oxygen species mediate the lipopolysaccharide-induced pro-inflammatory response in human gingival fibroblasts

    International Nuclear Information System (INIS)

    Li, Xue; Wang, Xiaoxuan; Zheng, Ming; Luan, Qing Xian

    2016-01-01

    Although periodontal diseases are initiated by bacteria that colonize the tooth surface and gingival sulcus, the host response is believed to play an essential role in the breakdown of connective tissue and bone. Mitochondrial reactive oxygen species (mtROS) have been proposed to regulate the activation of the inflammatory response by the innate immune system. However, the role of mtROS in modulating the response of human gingival fibroblasts (HGFs) to immune stimulation by lipopolysaccharides (LPS) has yet to be fully elucidated. Here, we showed that LPS from Porphyromonas gingivalis stimulated HGFs to increase mtROS production, which could be inhibited by treatment with a mitochondrial-targeted exogenous antioxidant (mito-TEMPO) or transfection with manganese superoxide dismutase (MnSOD). A time-course study revealed that an increase in the concentration of mtROS preceded the expression of inflammatory cytokines in HGFs. Mito-TEMPO treatment or MnSOD transfection also significantly prevented the LPS-induced increase of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Furthermore, suppressing LPS-induced mtROS generation inhibited the activation of p38, c-Jun N-terminal kinase, and inhibitor of nuclear factor-κB kinase, as well as the nuclear localization of nuclear factor-κB. These results demonstrate that mtROS generation is a key signaling event in the LPS-induced pro-inflammatory response of HGFs. - Highlights: • Inflammation is thought to promote pathogenic changes in periodontitis. • We investigated mtROS as a regulator of inflammation in gingival fibroblasts. • Targeted antioxidants were used to inhibit mtROS production after LPS challenge. • Inhibiting mtROS generation suppressed the secretion of pro-inflammatory cytokines. • JNK, p38, IKK, and NF-κB were shown to act as transducers of mtROS signaling.

  6. Evaluation of an Aqueous Extract from Horseradish Root (Armoracia rusticana Radix against Lipopolysaccharide-Induced Cellular Inflammation Reaction

    Directory of Open Access Journals (Sweden)

    Corinna Herz

    2017-01-01

    Full Text Available Horseradish (Armoracia rusticana is a perennial crop and its root is used in condiments. Traditionally, horseradish root is used to treat bacterial infections of the respiratory tract and urinary bladder. The antiphlogistic activity, determined in activated primary human peripheral blood mononuclear cells (PBMC, was evaluated for an aqueous extract and its subfractions, separated by HPLC. Compound analysis was done by UHPLC-QToF/MS and GC-MS. The aqueous extract concentration-dependently inhibited the anti-inflammatory response to lipopolysaccharide (LPS in terms of TNF-α release at ≥37 μg/mL. Further, the cyclooxygenase as well as lipoxygenase pathway was blocked by the extract as demonstrated by inhibition of COX-2 protein expression and PGE2 synthesis at ≥4 μg/mL and leukotriene LTB4 release. Mechanistic studies revealed that inhibition of ERK1/2 and c-Jun activation preceded COX-2 suppression upon plant extract treatment in the presence of LPS. Chemical analysis identified target compounds with a medium polarity as relevant for the observed bioactivity. Importantly, allyl isothiocyanate, which is quite well known for its anti-inflammatory capacity and as the principal pungent constituent in horseradish roots, was not relevant for the observations. The results suggest that horseradish root exerts an antiphlogistic activity in human immune cells by regulation of the COX and LOX pathway via MAPK signalling.

  7. Evaluation of an Aqueous Extract from Horseradish Root (Armoracia rusticana Radix) against Lipopolysaccharide-Induced Cellular Inflammation Reaction.

    Science.gov (United States)

    Herz, Corinna; Tran, Hoai Thi Thu; Márton, Melinda-Rita; Maul, Ronald; Baldermann, Susanne; Schreiner, Monika; Lamy, Evelyn

    2017-01-01

    Horseradish ( Armoracia rusticana ) is a perennial crop and its root is used in condiments. Traditionally, horseradish root is used to treat bacterial infections of the respiratory tract and urinary bladder. The antiphlogistic activity, determined in activated primary human peripheral blood mononuclear cells (PBMC), was evaluated for an aqueous extract and its subfractions, separated by HPLC. Compound analysis was done by UHPLC-QToF/MS and GC-MS. The aqueous extract concentration-dependently inhibited the anti-inflammatory response to lipopolysaccharide (LPS) in terms of TNF- α release at ≥37  μ g/mL. Further, the cyclooxygenase as well as lipoxygenase pathway was blocked by the extract as demonstrated by inhibition of COX-2 protein expression and PGE 2 synthesis at ≥4  μ g/mL and leukotriene LTB4 release. Mechanistic studies revealed that inhibition of ERK1/2 and c-Jun activation preceded COX-2 suppression upon plant extract treatment in the presence of LPS. Chemical analysis identified target compounds with a medium polarity as relevant for the observed bioactivity. Importantly, allyl isothiocyanate, which is quite well known for its anti-inflammatory capacity and as the principal pungent constituent in horseradish roots, was not relevant for the observations. The results suggest that horseradish root exerts an antiphlogistic activity in human immune cells by regulation of the COX and LOX pathway via MAPK signalling.

  8. 12-oxo-phytodienoic acid, a plant-derived oxylipin, attenuates lipopolysaccharide-induced inflammation in microglia

    Energy Technology Data Exchange (ETDEWEB)

    Taki-Nakano, Nozomi [Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan); Advanced Drug Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda, Saitama 335-8505 (Japan); Kotera, Jun [Advanced Drug Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda, Saitama 335-8505 (Japan); Ohta, Hiroyuki, E-mail: ohta.h.ab@m.titech.ac.jp [Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan); School of Life Science and Technology, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan)

    2016-05-13

    Jasmonates are plant lipid–derived oxylipins that act as key signaling compounds in plant immunity, germination, and development. Although some physiological activities of natural jasmonates in mammalian cells have been investigated, their anti-inflammatory actions in mammalian cells remain unclear. Here, we investigated whether jasmonates protect mouse microglial MG5 cells against lipopolysaccharide (LPS)–induced inflammation. Among the jasmonates tested, only 12-oxo-phytodienoic acid (OPDA) suppressed LPS-induced expression of the typical inflammatory cytokines interleukin-6 and tumor necrosis factor α. In addition, only OPDA reduced LPS-induced nitric oxide production through a decrease in the level of inducible nitric oxide synthase. Further mechanistic studies showed that OPDA suppressed neuroinflammation by inhibiting nuclear factor κB and p38 mitogen-activated protein kinase signaling in LPS-activated MG5 cells. In addition, OPDA induced expression of suppressor of cytokine signaling-1 (SOCS-1), a negative regulator of inflammation, in MG5 cells. Finally, we found that the nuclear factor erythroid 2-related factor 2 signaling cascade induced by OPDA is not involved in the anti-inflammatory effects of OPDA. These results demonstrate that OPDA inhibited LPS-induced cell inflammation in mouse microglial cells via multiple pathways, including suppression of nuclear factor κB, inhibition of p38, and activation of SOCS-1 signaling. -- Highlights: •OPDA attenuates LPS-induced inflammatory cytokines such as IL-6 and TNF-α. •OPDA reduces LPS-induced iNOS expression and NO production. •OPDA suppresses NF-κB and p38 pathways and activates SOCS-1 signaling.

  9. 12-oxo-phytodienoic acid, a plant-derived oxylipin, attenuates lipopolysaccharide-induced inflammation in microglia

    International Nuclear Information System (INIS)

    Taki-Nakano, Nozomi; Kotera, Jun; Ohta, Hiroyuki

    2016-01-01

    Jasmonates are plant lipid–derived oxylipins that act as key signaling compounds in plant immunity, germination, and development. Although some physiological activities of natural jasmonates in mammalian cells have been investigated, their anti-inflammatory actions in mammalian cells remain unclear. Here, we investigated whether jasmonates protect mouse microglial MG5 cells against lipopolysaccharide (LPS)–induced inflammation. Among the jasmonates tested, only 12-oxo-phytodienoic acid (OPDA) suppressed LPS-induced expression of the typical inflammatory cytokines interleukin-6 and tumor necrosis factor α. In addition, only OPDA reduced LPS-induced nitric oxide production through a decrease in the level of inducible nitric oxide synthase. Further mechanistic studies showed that OPDA suppressed neuroinflammation by inhibiting nuclear factor κB and p38 mitogen-activated protein kinase signaling in LPS-activated MG5 cells. In addition, OPDA induced expression of suppressor of cytokine signaling-1 (SOCS-1), a negative regulator of inflammation, in MG5 cells. Finally, we found that the nuclear factor erythroid 2-related factor 2 signaling cascade induced by OPDA is not involved in the anti-inflammatory effects of OPDA. These results demonstrate that OPDA inhibited LPS-induced cell inflammation in mouse microglial cells via multiple pathways, including suppression of nuclear factor κB, inhibition of p38, and activation of SOCS-1 signaling. -- Highlights: •OPDA attenuates LPS-induced inflammatory cytokines such as IL-6 and TNF-α. •OPDA reduces LPS-induced iNOS expression and NO production. •OPDA suppresses NF-κB and p38 pathways and activates SOCS-1 signaling.

  10. LFG-500, a newly synthesized flavonoid, attenuates lipopolysaccharide-induced acute lung injury and inflammation in mice.

    Science.gov (United States)

    Li, Chenglin; Yang, Dan; Cao, Xin; Wang, Fan; Jiang, Haijing; Guo, Hao; Du, Lei; Guo, Qinglong; Yin, Xiaoxing

    2016-08-01

    Acute lung injury (ALI) often causes significant morbidity and mortality worldwide. Improved treatment and effective strategies are still required for ALI patients. Our previous studies demonstrated that LFG-500, a novel synthesized flavonoid, has potent anti-cancer activities, while its anti-inflammatory effect has not been revealed. In the present study, the in vivo protective effect of LFG-500 on the amelioration of lipopolysaccharide (LPS)-induced ALI and inflammation was detected. LFG-500 attenuated LPS-induced histological alterations, suppressed the infiltration of inflammatory cells in lung tissues and bronchoalveolar lavage fluid, as well as inhibited the secretion of several inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in lung tissues after LPS challenge. In addition, the in vitro effects and mechanisms were studied in LPS stimulated RAW 264.7 cells and THP-1 cells. LFG-500 significantly decreased the secretion and expression of TNF-α, IL-1β, and IL-6 through inhibiting the transcriptional activation of NF-κB. Moreover, overexpression of NF-κB p65 reversed the inhibitory effect of LFG-500 on LPS-induced NF-κB activation and inflammatory cytokine secretion. Further elucidation of the mechanism revealed that p38 and JNK MAPK pathways were involved in the anti-inflammation effect of LFG-500, through which LFG-500 inhibited the classical IKK-dependent pathway and led to inactivation of NF-κB. More importantly, LFG-500 suppressed the expression and nuclear localization of NF-κB in LPS-induced ALI mice. Taken together, these results demonstrated that LFG-500 could attenuate LPS-induced ALI and inflammation by suppressing NF-κB activation, which provides new evidence for the anti-inflammation activity of LFG-500. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Dietary broccoli mildly improves neuroinflammation in aged mice but does not reduce lipopolysaccharide-induced sickness behavior.

    Science.gov (United States)

    Townsend, Brigitte E; Chen, Yung-Ju; Jeffery, Elizabeth H; Johnson, Rodney W

    2014-11-01

    Aging is associated with oxidative stress and heightened inflammatory response to infection. Dietary interventions to reduce these changes are therefore desirable. Broccoli contains glucoraphanin, which is converted to sulforaphane (SFN) by plant myrosinase during cooking preparation or digestion. Sulforaphane increases antioxidant enzymes including NAD(P)H quinone oxidoreductase and heme oxygenase I and inhibits inflammatory cytokines. We hypothesized that dietary broccoli would support an antioxidant response in brain and periphery of aged mice and inhibit lipopolysaccharide (LPS)-induced inflammation and sickness. Young adult and aged mice were fed control or 10% broccoli diet for 28 days before an intraperitoneal LPS injection. Social interactions were assessed 2, 4, 8, and 24 hours after LPS, and mRNA was quantified in liver and brain at 24 hours. Dietary broccoli did not ameliorate LPS-induced decrease in social interactions in young or aged mice. Interleukin-1β (IL-1β) expression was unaffected by broccoli consumption but was induced by LPS in brain and liver of adult and aged mice. In addition, IL-1β was elevated in brain of aged mice without LPS. Broccoli consumption decreased age-elevated cytochrome b-245 β, an oxidative stress marker, and reduced glial activation markers in aged mice. Collectively, these data suggest that 10% broccoli diet provides a modest reduction in age-related oxidative stress and glial reactivity, but is insufficient to inhibit LPS-induced inflammation. Thus, it is likely that SFN would need to be provided in supplement form to control the inflammatory response to LPS. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Expression of macrophage migration inhibitory factor and CD74 in the inner ear and middle ear in lipopolysaccharide-induced otitis media.

    Science.gov (United States)

    Ishihara, Hisashi; Kariya, Shin; Okano, Mitsuhiro; Zhao, Pengfei; Maeda, Yukihide; Nishizaki, Kazunori

    2016-10-01

    Significant expression of macrophage migration inhibitory factor and its receptor (CD74) was observed in both the middle ear and inner ear in experimental otitis media in mice. Modulation of macrophage migration inhibitory factor and its signaling pathway might be useful in the management of inner ear inflammation due to otitis media. Inner ear dysfunction secondary to otitis media has been reported. However, the specific mechanisms involved are not clearly understood. The aim of this study is to investigate the expression of macrophage migration inhibitory factor and CD74 in the middle ear and inner ear in lipopolysaccharide-induced otitis media. BALB/c mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline (PBS). The mice were sacrificed 24 h after injection, and temporal bones were processed for polymerase chain reaction (PCR) analysis, histologic examination, and immunohistochemistry. PCR examination revealed that the lipopolysaccharide-injected mice showed a significant up-regulation of macrophage migration inhibitory factor in both the middle ear and inner ear as compared with the PBS-injected control mice. The immunohistochemical study showed positive reactions for macrophage migration inhibitory factor and CD74 in infiltrating inflammatory cells, middle ear mucosa, and inner ear in the lipopolysaccharide-injected mice.

  13. Waste products of oilsands mine inhibit sex steroids in exposed fish

    International Nuclear Information System (INIS)

    Lister, A.; Van Der Kraak, G.J.; Nero, V.; Farwell, A.J.; Dixon, D.G.

    2002-01-01

    Mature fine tailings (MFT) and tailing pond water (TPW) are two of the wastes generated by oil sand mining operations at Syncrude Canada Ltd. in northern Alberta. A study was conducted to determine the impact of these wastes on reproductive steroid production in sexually mature goldfish. MFT is a toxic aqueous suspension consisting of organic acids, bitumen and metals. TPW is a saline solution consisting of both organic and inorganic contaminants. Goldfish were examined for 19 days in 3 of Syncrude's specially designed experimental ponds which were lined with or without MFT and capped with or without TPW. The study showed that plasma levels of testosterone and 17 β-estradiol in male and female fish in ponds with MFT but no TPW and ponds with both MFT and TPW were much lower compared to fish in a control pond with neither MFT nor TPW. The study also involved in vitro testis and ovarian incubations on the fish to determine potential differences in basal steroid production levels and how they react to gonadotropin. Results showed that gonadal tissues of fish from all ponds behaved similarly to the gonadotropin, thereby suggesting that under normal conditions, the oilsands wastes do not affect the ability of gonads to produce steroids. Compared to the control pond, both male and female fish from the pond with both MFT and TPW had significantly lower basal levels of testosterone, suggesting that the steroid inhibition could be caused at a site within the gonad. It was concluded that waste products of oilsands mining disrupt the reproductive endocrine system in goldfish

  14. Waste products of oilsands mine inhibit sex steroids in exposed fish

    Energy Technology Data Exchange (ETDEWEB)

    Lister, A.; Van Der Kraak, G.J. [Guelph Univ., ON (Canada); Nero, V.; Farwell, A.J.; Dixon, D.G. [Waterloo Univ., ON (Canada). Dept. of Biology

    2002-07-01

    Mature fine tailings (MFT) and tailing pond water (TPW) are two of the wastes generated by oil sand mining operations at Syncrude Canada Ltd. in northern Alberta. A study was conducted to determine the impact of these wastes on reproductive steroid production in sexually mature goldfish. MFT is a toxic aqueous suspension consisting of organic acids, bitumen and metals. TPW is a saline solution consisting of both organic and inorganic contaminants. Goldfish were examined for 19 days in 3 of Syncrude's specially designed experimental ponds which were lined with or without MFT and capped with or without TPW. The study showed that plasma levels of testosterone and 17 {beta}-estradiol in male and female fish in ponds with MFT but no TPW and ponds with both MFT and TPW were much lower compared to fish in a control pond with neither MFT nor TPW. The study also involved in vitro testis and ovarian incubations on the fish to determine potential differences in basal steroid production levels and how they react to gonadotropin. Results showed that gonadal tissues of fish from all ponds behaved similarly to the gonadotropin, thereby suggesting that under normal conditions, the oilsands wastes do not affect the ability of gonads to produce steroids. Compared to the control pond, both male and female fish from the pond with both MFT and TPW had significantly lower basal levels of testosterone, suggesting that the steroid inhibition could be caused at a site within the gonad. It was concluded that waste products of oilsands mining disrupt the reproductive endocrine system in goldfish.

  15. Krill Oil-In-Water Emulsion Protects against Lipopolysaccharide-Induced Proinflammatory Activation of Macrophages In Vitro.

    Science.gov (United States)

    Bonaterra, Gabriel A; Driscoll, David; Schwarzbach, Hans; Kinscherf, Ralf

    2017-03-15

    Parenteral nutrition is often a mandatory therapeutic strategy for cases of septicemia. Likewise, therapeutic application of anti-oxidants, anti-inflammatory therapy, and endotoxin lowering, by removal or inactivation, might be beneficial to ameliorate the systemic inflammatory response during the acute phases of critical illness. Concerning anti-inflammatory properties in this setting, omega-3 fatty acids of marine origin have been frequently described. This study investigated the anti-inflammatory and LPS-inactivating properties of krill oil (KO)-in-water emulsion in human macrophages in vitro. Differentiated THP-1 macrophages were activated using specific ultrapure-LPS that binds only on the toll-like receptor 4 (TLR4) in order to determine the inhibitory properties of the KO emulsion on the LPS-binding capacity, and the subsequent release of TNF-α. KO emulsion inhibited the macrophage binding of LPS to the TLR4 by 50% (at 12.5 µg/mL) and 75% (at 25 µg/mL), whereas, at 50 µg/mL, completely abolished the LPS binding. Moreover, KO (12.5 µg/mL, 25 µg/mL, or 50 µg/mL) also inhibited (30%, 40%, or 75%, respectively) the TNF-α release after activation with 0.01 µg/mL LPS in comparison with LPS treatment alone. KO emulsion influences the LPS-induced pro-inflammatory activation of macrophages, possibly due to inactivation of the LPS binding capacity.

  16. Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats.

    Science.gov (United States)

    Feng, Guang; Jiang, Ze-Yu; Sun, Bo; Fu, Jie; Li, Tian-Zuo

    2016-02-01

    Acute lung injury (ALI), a common component of systemic inflammatory disease, is a life-threatening condition without many effective treatments. Fisetin, a natural flavonoid from fruits and vegetables, was reported to have wide pharmacological properties such as anti-inflammatory, antioxidant, and anticancer activities. The aim of this study was to detect the effects of fisetin on lipopolysaccharide (LPS)-induced acute lung injury and investigate the potential mechanism. Fisetin was injected (1, 2, and 4 mg/kg, i.v.) 30 min before LPS administration (5 mg/kg, i.v.). Our results showed that fisetin effectively reduced the inflammatory cytokine release and total protein in bronchoalveolar lavage fluids (BALF), decreased the lung wet/dry ratios, and obviously improved the pulmonary histology in LPS-induced ALI. Furthermore, fisetin inhibited LPS-induced increases of neutrophils and macrophage infiltration and attenuated MPO activity in lung tissues. Additionally, fisetin could significantly inhibit the Toll-like receptor 4 (TLR4) expression and the activation of NF-κB in lung tissues. Our data indicates that fisetin has a protective effect against LPS-induced ALI via suppression of TLR4-mediated NF-κB signaling pathways, and fisetin may be a promising candidate for LPS-induced ALI treatment.

  17. Carbon monoxide alleviates lipopolysaccharide-induced oxidative stress injury through suppressing the expression of Fis1 in NR8383 cells

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Jia [Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100 (China); Yu, Jian-bo, E-mail: yujianbo11@126.com [Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100 (China); Liu, Wei; Wang, Dan; Zhang, Yuan; Gong, Li-rong; Dong, Shu-an [Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100 (China); Liu, Da-quan [Department of Pharmacology, Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Tianjin 300100 (China)

    2016-11-15

    Acute respiratory distress syndrome (ARDS) is one of the most devastating complications of sepsis lacking of effective therapy. Mitochondrial dynamics undergoing continuous fusion and fission play a crucial role in mitochondrial structure and function. Fis1, as a small protein located on the outer membrane of mitochondria, has been thought to be an important protein mediated mitochondrial fission. During ARDS, alveolar macrophages suffer from increased oxidative stress and apoptosis, and also accompanied by disrupted mitochondrial dynamics. In addition, as one of the products of heme degradation catalyzed by heme oxygenase, carbon monoxide (CO) possesses powerful protective properties in vivo or in vitro models, such as anti-inflammatory, antioxidant and anti-apoptosis function. However, there is little evidence that CO alleviates oxidative stress damage through altering mitochondrial fission in alveolar macrophages. In the present study, our results showed that CO increased cell vitality, improved mitochondrial SOD activity, reduced reactive oxygen species (ROS) production and inhibited cell apoptosis in NR8383 exposed to LPS. Meanwhile, CO decreased the expression of Fis1, increased mitochondrial membrane potential and sustained elongation of mitochondria in LPS-incubated NR8383. Overall, our study underscored a critical role of CO in suppressing the expression of Fis1 and alleviating LPS- induced oxidative stress damage in alveolar macrophages. - Highlights: • LPS exposure triggered cell injury in NR8383. • CO alleviated LPS-induced oxidative stress damage in alveolar macrophages. • CO inhibited Fis1 levels and improved mitochondrial function in LPS-induced NR8383.

  18. Chemomics-Integrated Proteomics Analysis of Jie-Geng-Tang to Ameliorate Lipopolysaccharide-Induced Acute Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Jin Tao

    2016-01-01

    Full Text Available Jie-Geng-Tang (JGT, a classic and famous traditional Chinese medicine (TCM prescription composed of Platycodon grandiflorum (Jacq. A. DC. (PG and Glycyrrhiza uralensis Fisch. (GU, is well known for “clearing heat and relieving toxicity” and its ability to “diffuse the lung and relieve sore throat.” However, the mechanism underlying its action remains unclear. In this study, potential anti-inflammatory ingredients were screened and submitted to PharmMapper and the KEGG bioinformatics website to predict the target proteins and related pathways, respectively. Differentially expressed candidate proteins from acute lung injury (ALI mice treated with JGT were identified by isobaric tags for relative and absolute quantitation (iTRAQ and LC Triple-TOF. Eleven potential anti-inflammatory ingredients were found, including the derivatives of glycyrrhizic acid, licorice-saponin, liquiritin, and platycodigenin. A total of sixty-seven differentially expressed proteins were confirmed after JGT treatment with four therapeutic functions, including immunoregulation, anti-inflammation, ribosome, and muscle contraction. PG and GU comediate PI3K/Akt signal pathway inhibition of NF-κB, VCAM1, and ICAM1 release which primarily act on PI3K, PDK1, AKT, and GSK3β. GU markedly inhibits the ERK/MAPK signaling pathways and primarily acts on LCK, RAS, and MEK. A network was constructed using bioactive ingredients, targets, and pathways to determine the mechanism underlying JGT treatment of ALI.

  19. Effect of Egg White Combined with Chalcanthite on Lipopolysaccharide induced Inflammatory Cytokine Expression in RAW 264.7 cells

    Directory of Open Access Journals (Sweden)

    Choi Eun-A

    2012-03-01

    Full Text Available Historically, mineral compound herbal medicines have long been used in treatments of immune-related diseases in Korea, China and other Asian countries. In this study, we inv-estigated the anti-inflammatory effect of egg white combined with chalcanthite (IS4 on lipopolysaccharide (LPS-stimulated RAW 264.7 cells. RAW 264.7 cells cultured with LPS and various con-centrations of IS4 were analyzed to determine the production of pro-inflammatory cytokines and mediators by using enzyme-linked immune sorbent assays (ELISAs. IS4 concentration inhibited the production of interleukin-1beta (IL-1β, interleukin-6 (IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF induced by LPS. IS4 at high concentrations (25 and 50`㎍/ml inhibited, in concentration-dependent manner, the expression of tumor necrosis factor-alpha (TNF–α stimulated by LPS. IS4 has shown an anti-inflammatory effect in RAW 264.7 cells.

  20. Lipopolysaccharide-induced inflammation attenuates taste progenitor cell proliferation and shortens the life span of taste bud cells

    Directory of Open Access Journals (Sweden)

    Brand Joseph

    2010-06-01

    Full Text Available Abstract Background The mammalian taste bud, a complex collection of taste sensory cells, supporting cells, and immature basal cells, is the structural unit for detecting taste stimuli in the oral cavity. Even though the cells of the taste bud undergo constant turnover, the structural homeostasis of the bud is maintained by balancing cell proliferation and cell death. Compared with nongustatory lingual epithelial cells, taste cells express higher levels of several inflammatory receptors and signalling proteins. Whether inflammation, an underlying condition in some diseases associated with taste disorders, interferes with taste cell renewal and turnover is unknown. Here we report the effects of lipopolysaccharide (LPS-induced inflammation on taste progenitor cell proliferation and taste bud cell turnover in mouse taste tissues. Results Intraperitoneal injection of LPS rapidly induced expression of several inflammatory cytokines, including tumor necrosis factor (TNF-α, interferon (IFN-γ, and interleukin (IL-6, in mouse circumvallate and foliate papillae. TNF-α and IFN-γ immunoreactivities were preferentially localized to subsets of cells in taste buds. LPS-induced inflammation significantly reduced the number of 5-bromo-2'-deoxyuridine (BrdU-labeled newborn taste bud cells 1-3 days after LPS injection, suggesting an inhibition of taste bud cell renewal. BrdU pulse-chase experiments showed that BrdU-labeled taste cells had a shorter average life span in LPS-treated mice than in controls. To investigate whether LPS inhibits taste cell renewal by suppressing taste progenitor cell proliferation, we studied the expression of Ki67, a cell proliferation marker. Quantitative real-time RT-PCR revealed that LPS markedly reduced Ki67 mRNA levels in circumvallate and foliate epithelia. Immunofluorescent staining using anti-Ki67 antibodies showed that LPS decreased the number of Ki67-positive cells in the basal regions surrounding circumvallate taste buds

  1. Lipopolysaccharide-induced inflammation attenuates taste progenitor cell proliferation and shortens the life span of taste bud cells.

    Science.gov (United States)

    Cohn, Zachary J; Kim, Agnes; Huang, Liquan; Brand, Joseph; Wang, Hong

    2010-06-10

    The mammalian taste bud, a complex collection of taste sensory cells, supporting cells, and immature basal cells, is the structural unit for detecting taste stimuli in the oral cavity. Even though the cells of the taste bud undergo constant turnover, the structural homeostasis of the bud is maintained by balancing cell proliferation and cell death. Compared with nongustatory lingual epithelial cells, taste cells express higher levels of several inflammatory receptors and signalling proteins. Whether inflammation, an underlying condition in some diseases associated with taste disorders, interferes with taste cell renewal and turnover is unknown. Here we report the effects of lipopolysaccharide (LPS)-induced inflammation on taste progenitor cell proliferation and taste bud cell turnover in mouse taste tissues. Intraperitoneal injection of LPS rapidly induced expression of several inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-6, in mouse circumvallate and foliate papillae. TNF-alpha and IFN-gamma immunoreactivities were preferentially localized to subsets of cells in taste buds. LPS-induced inflammation significantly reduced the number of 5-bromo-2'-deoxyuridine (BrdU)-labeled newborn taste bud cells 1-3 days after LPS injection, suggesting an inhibition of taste bud cell renewal. BrdU pulse-chase experiments showed that BrdU-labeled taste cells had a shorter average life span in LPS-treated mice than in controls. To investigate whether LPS inhibits taste cell renewal by suppressing taste progenitor cell proliferation, we studied the expression of Ki67, a cell proliferation marker. Quantitative real-time RT-PCR revealed that LPS markedly reduced Ki67 mRNA levels in circumvallate and foliate epithelia. Immunofluorescent staining using anti-Ki67 antibodies showed that LPS decreased the number of Ki67-positive cells in the basal regions surrounding circumvallate taste buds, the niche for taste progenitor

  2. Intervention effect and dose-dependent response of tanreqing injection on airway inflammation in lipopolysaccharide-induced rats.

    Science.gov (United States)

    Dong, Shoujin; Zhong, Yunqing; Yang, Kun; Xiong, Xiaoling; Mao, Bing

    2013-08-01

    To assess the effect of Tanreqing injection on airway inflammation in rats. A rat model of airway inflammation was generated with lipopolysaccharide (LPS). Tanreqing injection was given by intratracheal instillation, and bronchoalveolar lavage fluid (BALF) from the right lung was collected. BALF total cell and neutrophil counts were then determined. In addition, BALF levels of inflammatory cytokines interleukin-13, cytokine-induced neutrophil chemoat-tractant-1, and tumor necrosis factor-alpha were measured using enzyme linked immunosorbent assay. The middle lobe of the right lung was stained with hematoxylin-eosin and histological changes examined. LPS increased airway inflammation, decreased BALF inflammatory cell count, inflammatory cytokine levels, and suppressed leukocyte influx of the lung. The LPS-induced airway inflammation peaked at 24 h, decreased beginning at 48 h, and had decreased markedly by 96 h. Tanreqing injection contains anti-inflammatory properties, and inhibits airway inflammation in a dose-dependent manner.

  3. Selol, an organic selenium donor, prevents lipopolysaccharide-induced oxidative stress and inflammatory reaction in the rat brain.

    Science.gov (United States)

    Dominiak, Agnieszka; Wilkaniec, Anna; Jęśko, Henryk; Czapski, Grzegorz A; Lenkiewicz, Anna M; Kurek, Eliza; Wroczyński, Piotr; Adamczyk, Agata

    2017-09-01

    Neuroinflammation and oxidative stress are key intertwined pathological factors in many neurological, particularly neurodegenerative diseases, such as Alzheimer's and Parkinson's disorders as well as autism. The present study was conducted to evaluate the protective effects of Selol, an organic selenium donor, against lipopolysaccharide (LPS)-mediated inflammation in rat brain. The results demonstrated that the peripheral administration of LPS in a dose of 100 μg/kg b.w. evoked typical pathological reaction known as systemic inflammatory response. Moreover, we observed elevated blood levels of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress, as well as increased concentration of tumor necrosis factor-α (TNF-α) in LPS-treated animals. Selol significantly prevented these LPS-evoked changes. Subsequently, Selol protected against LPS-induced up-regulation of proinflammatory cytokines (Tnfa, Ifng, Il6) in rat brain cortex. The molecular mechanisms through which Selol prevented the neuroinflammation were associated with the inhibition of oxidized glutathione (GSSG) accumulation and with an increase of glutathione-associated enzymes: glutathione peroxidase (Se-GPx), glutathione reductase (GR) as well as thioredoxin reductase (TrxR) activity and expression. Finally, we observed that Selol administration effectively protected against LPS-induced changes in the expression of brain-derived neurotrophic factor (Bdnf). In conclusion, our studies indicated that Selol effectively protects against LPS-induced neuroinflammation by inhibiting pro-inflammatory cytokine release, by boosting antioxidant systems, and by augmenting BDNF level. Therefore, Selol could be a multi-potent and effective drug useful in the treatment and prevention of brain disorders associated with neuroinflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Krill Oil-In-Water Emulsion Protects against Lipopolysaccharide-Induced Proinflammatory Activation of Macrophages In Vitro

    Directory of Open Access Journals (Sweden)

    Gabriel A. Bonaterra

    2017-03-01

    Full Text Available Background: Parenteral nutrition is often a mandatory therapeutic strategy for cases of septicemia. Likewise, therapeutic application of anti-oxidants, anti-inflammatory therapy, and endotoxin lowering, by removal or inactivation, might be beneficial to ameliorate the systemic inflammatory response during the acute phases of critical illness. Concerning anti-inflammatory properties in this setting, omega-3 fatty acids of marine origin have been frequently described. This study investigated the anti-inflammatory and LPS-inactivating properties of krill oil (KO-in-water emulsion in human macrophages in vitro. Materials and Methods: Differentiated THP-1 macrophages were activated using specific ultrapure-LPS that binds only on the toll-like receptor 4 (TLR4 in order to determine the inhibitory properties of the KO emulsion on the LPS-binding capacity, and the subsequent release of TNF-α. Results: KO emulsion inhibited the macrophage binding of LPS to the TLR4 by 50% (at 12.5 µg/mL and 75% (at 25 µg/mL, whereas, at 50 µg/mL, completely abolished the LPS binding. Moreover, KO (12.5 µg/mL, 25 µg/mL, or 50 µg/mL also inhibited (30%, 40%, or 75%, respectively the TNF-α release after activation with 0.01 µg/mL LPS in comparison with LPS treatment alone. Conclusion: KO emulsion influences the LPS-induced pro-inflammatory activation of macrophages, possibly due to inactivation of the LPS binding capacity.

  5. Lipopolysaccharide induces proliferation and osteogenic differentiation of adipose-derived mesenchymal stromal cells in vitro via TLR4 activation

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    Herzmann, Nicole; Salamon, Achim [Department of Cell Biology, University Medicine Rostock, Schillingallee 69, D-18057 Rostock (Germany); Fiedler, Tomas [Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, Schillingallee 70, D-18057 Rostock (Germany); Peters, Kirsten, E-mail: kirsten.peters@med.uni-rostock.de [Department of Cell Biology, University Medicine Rostock, Schillingallee 69, D-18057 Rostock (Germany)

    2017-01-01

    Multipotent mesenchymal stromal cells (MSC) are capable of multi-lineage differentiation and support regenerative processes. In bacterial infections, resident MSC can come intocontact with and need to react to bacterial components. Lipopolysaccharide (LPS), a typical structure of Gram-negative bacteria, increases the proliferation and osteogenic differentiation of MSC. LPS is usually recognized by the toll-like receptor (TLR) 4 and induces pro-inflammatory reactions in numerous cell types. In this study, we quantified the protein expression of TLR4 and CD14 on adipose-derived MSC (adMSC) in osteogenic differentiation and investigated the effect of TLR4 activation by LPS on NF-κB activation, proliferation and osteogenic differentiation of adMSC. We found that TLR4 is expressed on adMSC whereas CD14 is not, and that osteogenic differentiation induced an increase of the amount of TLR4 protein whereas LPS stimulation did not. Moreover, we could show that NF-κB activation via TLR4 occurs upon LPS treatment. Furthermore, we were able to show that competitive inhibition of TLR4 completely abolished the stimulatory effect of LPS on the proliferation and osteogenic differentiation of adMSC. In addition, the inhibition of TLR4 leads to the complete absence of osteogenic differentiation of adMSC, even when osteogenically stimulated. Thus, we conclude that LPS induces proliferation and osteogenic differentiation of adMSC in vitro through the activation of TLR4 and that the TLR4 receptor seems to play a role during osteogenic differentiation of adMSC.

  6. Prenylated Flavonoids from Morus alba L. Cause Inhibition of G1/S Transition in THP-1 Human Leukemia Cells and Prevent the Lipopolysaccharide-Induced Inflammatory Response

    Czech Academy of Sciences Publication Activity Database

    Kollár, P.; Bárta, T.; Hošek, J.; Souček, Karel; Závalová, V.; Artinian, S.; Talhouk, R.; Smejkal, K.; Suchý, P.; Hampl, A.

    2013-01-01

    Roč. 2013, č. 2013 (2013) ISSN 1741-427X Grant - others:GA MŠk(CZ) ED1.100/02/0123 Institutional support: RVO:68081707 Keywords : ROOT BARK * DIMETHYL-SULFOXIDE * IN-VITRO Subject RIV: BO - Biophysics Impact factor: 2.175, year: 2013

  7. Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF-kappaB-independent mechanism.

    Science.gov (United States)

    Birrell, M A; McCluskie, K; Wong, S; Donnelly, L E; Barnes, P J; Belvisi, M G

    2005-05-01

    Consumption of a naturally occurring polyphenol, resveratrol, in particular through drinking moderate amounts of red wine, has been suggested to be beneficial to health. A plethora of in vitro studies published demonstrate various anti-inflammatory actions of resveratrol. The aim of this research was to determine whether any of these anti-inflammatory effects translate in vivo in a rodent model of LPS induced airway inflammation. Resveratrol reduced lung tissue neutrophilia to a similar magnitude as that achieved by treatment with budesonide. This was associated with a reduction in pro-inflammatory cytokines and prostanoid levels. Interestingly, the reduction did not appear to be due to an impact on NF-kappaB activation or the expression of the respective genes as suggested by various in vitro publications. These results suggest that resveratrol may possess anti-inflammatory properties via a novel mechanism. Elucidation of this mechanism may lead to potential new therapies for the treatment of chronic inflammation.

  8. Prenylated Flavonoids from Morus alba L. Cause Inhibition of G1/S Transition in THP-1 Human Leukemia Cells and Prevent the Lipopolysaccharide-Induced Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Peter Kollar

    2013-01-01

    Full Text Available Morus alba L. (MA is a natural source of many compounds with different biological effects. It has been described to possess anti-inflammatory, antioxidant, and hepatoprotective activities. The aim of this study was to evaluate cytotoxicity of three flavonoids isolated from MA (kuwanon E, cudraflavone B, and 4′-O-methylkuwanon E and to determine their effects on proliferation of THP-1 cells, and on cell cycle progression of cancer cells. Anti-inflammatory effects were also determined for all three given flavonoids. Methods used in the study included quantification of cells by hemocytometer and WST-1 assays, flow cytometry, western blotting, ELISA, and zymography. From the three compounds tested, cudraflavone B showed the strongest effects on cell cycle progression and viability of tumor and/or immortalized cells and also on inflammatory response of macrophage-like cells. Kuwanon E and 4′-O-methylkuwanon E exerted more sophisticated rather than direct toxic effect on used cell types. Our data indicate that mechanisms different from stress-related or apoptotic signaling pathways are involved in the action of these compounds. Although further studies are required to precisely define the mechanisms of MA flavonoid action in human cancer and macrophage-like cells, here we demonstrate their effects combining antiproliferative and anti-inflammatory activities, respectively.

  9. Glaucocalyxin B Alleviates Lipopolysaccharide-Induced Parkinson’s Disease by Inhibiting TLR/NF-κB and Activating Nrf2/HO-1 Pathway

    Directory of Open Access Journals (Sweden)

    Wei Xu

    2017-12-01

    Full Text Available Background/Aims: Parkinson’s disease (PD is a common neurodegenerative disease in the old population, characterized by dopaminergic neuron loss, inflammation and oxidative stress injury in the substantia nigra. Glaucocalyxin B (GLB, an ent-kauranoid diterpenoid isolated from Rabdosia japonica, has anti-inflammation and anti-tumor effects. However, its effects on PD remain unclear. Methods: PD was introduced in rats via injection of lipopolysaccharide (LPS into cerebral corpus striatum, and GLB was given intracerebroventricularly to these rats. Their walking, climbing and sensory states were detected by Stepping, Whisker and Cylinder Tests. The expression of tyrosine hydroxylase (TH, glial fibrillary acidic protein (GFAP, CD11b and ionized calcium binding adaptor molecule (IBA-1 were detected by immunohischemical staining. The levels of a series of inflammatory factors, oxidative stress-related factors and apoptosis-related factors were measured by real-time PCR, immunoblotting and ELISA. In addition, Toll-like receptor (TLR/nuclear factor kappa B (NF-κB and nuclear factor erythroid 2-related factor 2 (Nrf2/heme oxygenase (HO-1 pathways were investigated to illustrate the underlying mechanism. In vitro, microglial cells exposed to LPS were treated with GLB. Results: The injection of LPS caused walking, climbing and sensory disturbances in rats, induced inflammation, oxidative stress response and apoptosis, and activated TLR/NF-κB and Nrf2/ HO-1 pathways in the cerebral tissue. GLB administration attenuated LPS-induced alterations. The TLR/NF-κB pathway was deactivated and Nrf2/HO-1 was activated after application of GLB. In vitro, cytotoxic effects induced by the conditioned medium derived from microglial cells exposed to LPS in PC12 cells were attenuated by GLB. Conclusion: GLB suppresses LPS-induced PD symptoms by modification of TLR/NF-κB and Nrf2/HO-1 pathways in vivo and in vitro.

  10. Inhibition of Lipopolysaccharide-Induced Interleukin 8 in Human Adenocarcinoma Cell Line HT-29 by Spore Probiotics: B. coagulans and B. subtilis (natto).

    Science.gov (United States)

    Azimirad, Masoumeh; Alebouyeh, Masoud; Naji, Tahereh

    2017-03-01

    Probiotics are used as a treatment for different intestinal disorders. They confer health benefits by different ways. This study was aimed to investigate immunomodulatory effect of Bacillus probiotic spores on the production of lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) in HT-29 intestinal epithelial cells. Differentiated intestinal epithelial cell line was used as a model for the study of colonization of purified spores (Bacillus subtilis (natto) and B. coagulans) and their anti-inflammatory effects. MTT assay and trypan blue staining were used for the detection of optimal concentration of the purified spores and LPS. Pre-treatment assay was done by treatment of the cells with the purified spores for 2 h, followed by challenges with LPS for 3 and 18 h. Post-treatment assay was done by initial treatment of the cells with LPS for 18 h, followed by the spores for 3 and 6 h. Levels of IL-8 secretion and its mRNA expression were measured by ELISA and relative Q real-time PCR. Our results showed similar rates of adherence to intestinal epithelial cells by the spore probiotics, while displaying no cytotoxic effect. In the pre-treatment assay, a significant decrease in IL-8, at both protein and mRNA levels, was measured for B. coagulans spores after the addition of LPS, which was higher than those observed for Bacillus subtilis (natto) spores. In the post-treatment assay, while Bacillus subtilis (but not B. coagulans) diminished the LPS-stimulated IL-8 levels after 3 h of incubation, the inhibitory effect was not constant. In conclusion, ability of Bacillus spore probiotics for adherence to intestinal epithelial cell and their anti-inflammatory effects, through interference with LPS/IL-8 signaling, was shown in this study. Further studies are needed to characterize responsible bacterial compounds associated with these effects.

  11. Methyl Gallate Inhibits Osteoclast Formation and Function by Suppressing Akt and Btk-PLCγ2-Ca2+ Signaling and Prevents Lipopolysaccharide-Induced Bone Loss.

    Science.gov (United States)

    Baek, Jong Min; Kim, Ju-Young; Lee, Chang Hoon; Yoon, Kwon-Ha; Lee, Myeung Su

    2017-03-07

    In the field of bone research, various natural derivatives have emerged as candidates for osteoporosis treatment by targeting abnormally elevated osteoclastic activity. Methyl gallate, a plant-derived phenolic compound, is known to have numerous pharmacological effects against inflammation, oxidation, and cancer. Our purpose was to explore the relation between methyl gallate and bone metabolism. Herein, we performed screening using methyl gallate by tartrate resistant acid phosphatase (TRAP) staining and revealed intracellular mechanisms responsible for methyl gallate-mediated regulation of osteoclastogenesis by Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR). Furthermore, we assessed the effects of methyl gallate on the characteristics of mature osteoclasts. We found that methyl gallate significantly suppressed osteoclast formation through Akt and Btk-PLCγ2-Ca 2+ signaling. The blockade of these pathways was confirmed through transduction of cells with a CA-Akt retrovirus and evaluation of Ca 2+ influx intensity (staining with Fluo-3/AM). Indeed, methyl gallate downregulated the formation of actin ring-positive osteoclasts and resorption pit areas. In agreement with in vitro results, we found that administration of methyl gallate restored osteoporotic phenotype stimulated by acute systemic injection of lipopolysaccharide in vivo according to micro-computed tomography and histological analysis. Our data strongly indicate that methyl gallate may be useful for the development of a plant-based antiosteoporotic agent.

  12. Rosiglitazone, a Peroxisome Proliferator-Activated Receptor (PPAR)-γ Agonist, Attenuates Inflammation Via NF-κB Inhibition in Lipopolysaccharide-Induced Peritonitis.

    Science.gov (United States)

    Zhang, Yun-Fang; Zou, Xun-Liang; Wu, Jun; Yu, Xue-Qing; Yang, Xiao

    2015-12-01

    We assessed the anti-inflammatory effect of peroxisome proliferator-activated receptor (PPAR)-γ agonist, rosiglitazone, in a lipopolysaccharide (LPS)-induced peritonitis rat model. LPS was intraperitoneally injected into rats to establish peritonitis model. Male Sprague-Dawley (SD) rats were assigned to normal saline (the solvent of LPS), LPS, rosiglitazone plus LPS, and rosiglitazone alone. A simple peritoneal equilibrium test was performed with 20 ml 4.25 % peritoneal dialysis fluid. We measured the leukocyte count in dialysate and ultrafiltration volume. Peritoneal membrane histochemical staining was performed, and peritoneal thickness was assessed. CD40 and intercellular adhesion molecule-1 messenger RNA (ICAM-1 mRNA) levels in rat visceral peritoneum were detected by reverse transcription (RT)-PCR. IL-6 in rat peritoneal dialysis effluent was measured using enzyme-linked immunosorbent assay. The phosphorylation of NF-κB-p65 and IκBα was analyzed by Western blot. LPS administration resulted in increased peritoneal thickness and decreased ultrafiltration volume. Rosiglitazone pretreatment significantly decreased peritoneal thickness. In addition to CD40 and ICAM-1 mRNA expression, the IL-6, p-p65, and p-IκBα protein expressions were enhanced in LPS-administered animals. Rosiglitazone pretreatment significantly decreased ICAM-1 mRNA upregulation, secretion of IL-6 protein, and phosphorylation of NF-κB-p65 and IκBα without decreasing CD40 mRNA expression. Rosiglitazone has a protective effect in peritonitis, simultaneously decreasing NF-κB phosphorylation, suggesting that NF-κB signaling pathway mediated peritoneal inflammation induced by LPS. PPAR-γ might be considered a potential therapeutic target against peritonitis.

  13. Fucofuroeckol-A from Eisenia bicyclis Inhibits Inflammation in Lipopolysaccharide-Induced Mouse Macrophages via Downregulation of the MAPK/NF-κB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Sang-Hoon Lee

    2016-01-01

    Full Text Available Fucofuroeckol-A (FF isolated from an edible perennial brown seaweed Eisenia bicyclis was shown to be potent anti-inflammatory agents. FF suppressed the production of nitric oxide (NO and prostaglandin E2 (PGE2 and the expression of inducible nitric oxide synthase and cyclooxygenase-2 dose dependently in lipopolysaccharide- (LPS- induced RAW 264.7 mouse macrophages. An enzyme-linked immunosorbent assay and cytometric bead array assay demonstrated that FF significantly reduced the production of proinflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, and that of the monocyte chemoattractant protein-1. Moreover, FF reduced the activation of nuclear factor κB (NF-κB and mitogen-activated protein kinases (MAPKs. These results strongly suggest that the inhibitory effects of fucofuroeckol-A from E. bicyclis on LPS-induced NO and PGE2 production might be due to the suppression of the NF-κB and MAPK signaling pathway.

  14. Methyl Gallate Inhibits Osteoclast Formation and Function by Suppressing Akt and Btk-PLCγ2-Ca2+ Signaling and Prevents Lipopolysaccharide-Induced Bone Loss

    Directory of Open Access Journals (Sweden)

    Jong Min Baek

    2017-03-01

    Full Text Available In the field of bone research, various natural derivatives have emerged as candidates for osteoporosis treatment by targeting abnormally elevated osteoclastic activity. Methyl gallate, a plant-derived phenolic compound, is known to have numerous pharmacological effects against inflammation, oxidation, and cancer. Our purpose was to explore the relation between methyl gallate and bone metabolism. Herein, we performed screening using methyl gallate by tartrate resistant acid phosphatase (TRAP staining and revealed intracellular mechanisms responsible for methyl gallate-mediated regulation of osteoclastogenesis by Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR. Furthermore, we assessed the effects of methyl gallate on the characteristics of mature osteoclasts. We found that methyl gallate significantly suppressed osteoclast formation through Akt and Btk-PLCγ2-Ca2+ signaling. The blockade of these pathways was confirmed through transduction of cells with a CA-Akt retrovirus and evaluation of Ca2+ influx intensity (staining with Fluo-3/AM. Indeed, methyl gallate downregulated the formation of actin ring-positive osteoclasts and resorption pit areas. In agreement with in vitro results, we found that administration of methyl gallate restored osteoporotic phenotype stimulated by acute systemic injection of lipopolysaccharide in vivo according to micro-computed tomography and histological analysis. Our data strongly indicate that methyl gallate may be useful for the development of a plant-based antiosteoporotic agent.

  15. Butyrate attenuates lipopolysaccharide-induced inflammation in intestinal cells and Crohn's mucosa through modulation of antioxidant defense machinery.

    Directory of Open Access Journals (Sweden)

    Ilaria Russo

    Full Text Available Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease (IBD, including Crohn's disease (CrD. High levels of Reactive Oxygen Species (ROS induce the activation of the redox-sensitive nuclear transcription factor kappa-B (NF-κB, which in turn triggers the inflammatory mediators. Butyrate decreases pro-inflammatory cytokine expression by the lamina propria mononuclear cells in CrD patients via inhibition of NF-κB activation, but how it reduces inflammation is still unclear. We suggest that butyrate controls ROS mediated NF-κB activation and thus mucosal inflammation in intestinal epithelial cells and in CrD colonic mucosa by triggering intracellular antioxidant defense systems. Intestinal epithelial Caco-2 cells and colonic mucosa from 14 patients with CrD and 12 controls were challenged with or without lipopolysaccaride from Escherichia coli (EC-LPS in presence or absence of butyrate for 4 and 24 h. The effects of butyrate on oxidative stress, p42/44 MAP kinase phosphorylation, p65-NF-κB activation and mucosal inflammation were investigated by real time PCR, western blot and confocal microscopy. Our results suggest that EC-LPS challenge induces a decrease in Gluthation-S-Transferase-alpha (GSTA1/A2 mRNA levels, protein expression and catalytic activity; enhanced levels of ROS induced by EC-LPS challenge mediates p65-NF-κB activation and inflammatory response in Caco-2 cells and in CrD colonic mucosa. Furthermore butyrate treatment was seen to restore GSTA1/A2 mRNA levels, protein expression and catalytic activity and to control NF-κB activation, COX-2, ICAM-1 and the release of pro-inflammatory cytokine. In conclusion, butyrate rescues the redox machinery and controls the intracellular ROS balance thus switching off EC-LPS induced inflammatory response in intestinal epithelial cells and in CrD colonic mucosa.

  16. Effect of penehyclidine hydrochloride on β-arrestin-1 expression in lipopolysaccharide-induced human pulmonary microvascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhan, J. [Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei (China); Xiao, F. [Department of Osteology, Pu Ai Hospital, Huazhong University of Science and Technology, Wuhan, Hubei (China); Zhang, Z.Z.; Wang, Y.P.; Chen, K.; Wang, Y.L. [Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei (China)

    2013-12-02

    β-arrestins are expressed proteins that were first described, and are well-known, as negative regulators of G protein-coupled receptor signaling. Penehyclidine hydrochloride (PHC) is a new anti-cholinergic drug that can inhibit biomembrane lipid peroxidation, and decrease cytokines and oxyradicals. However, to date, no reports on the effects of PHC on β-arrestin-1 in cells have been published. The aim of this study was to investigate the effect of PHC on β-arrestin-1 expression in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMEC). Cultured HPMEC were pretreated with PHC, followed by LPS treatment. Muscarinic receptor mRNAs were assayed by real-time quantitative PCR. Cell viability was assayed by the methyl thiazolyl tetrazolium (MTT) conversion test. The dose and time effects of PHC on β-arrestin-1 expression in LPS-induced HPMEC were determined by Western blot analysis. Cell malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured. It was found that the M{sub 3} receptor was the one most highly expressed, and was activated 5 min after LPS challenge. Furthermore, 2 μg/mL PHC significantly upregulated expression of β-arrestin-1 within 10 to 15 min. Compared with the control group, MDA levels in cells were remarkably increased and SOD activities were significantly decreased in LPS pretreated cells, while PHC markedly decreased MDA levels and increased SOD activities. We conclude that PHC attenuated ROS injury by upregulating β-arrestin-1 expression, thereby implicating a mechanism by which PHC may exert its protective effects against LPS-induced pulmonary microvascular endothelial cell injury.

  17. Lipopolysaccharide-Induced Behavioral Alterations Are Alleviated by Sodium Phenylbutyrate via Attenuation of Oxidative Stress and Neuroinflammatory Cascade.

    Science.gov (United States)

    Jangra, Ashok; Sriram, Chandra Shaker; Lahkar, Mangala

    2016-08-01

    Oxido-nitrosative stress, neuroinflammation, and reduced level of neurotrophins are implicated in the pathophysiology of anxiety and depressive illness. A few recent studies have revealed the role of endoplasmic reticulum (ER) stress in the pathophysiology of stress and depression. The aim of the present study is to investigate the neuroprotective potential of sodium phenylbutyrate (SPB), an ER stress inhibitor against lipopolysaccharide (LPS)-induced anxiety and depressive-like behavior in Swiss albino mice. Anxiety and depressive-like behavior was induced by LPS (0.83 mg/kg; i.p.) administration. Various behavioral tests were conducted to evaluate the anxiety and depressive-like behavior in mice. Real-time PCR was employed for the detection and expression of ER stress markers (78-kDa glucose-regulated protein (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)). Pretreatment with SPB significantly ameliorated the LPS-induced anxiety and depressive-like behavior as revealed by behavioral paradigm results. LPS-induced oxidative stress was ameliorated by SPB pretreatment in hippocampus (HC) and prefrontal cortex (PFC) region. Neuroinflammation was significantly reduced by SPB pretreatment in LPS-treated mice as evident from reduction in proinflammatory cytokines (IL-1β and TNF-α). Importantly, LPS administration significantly up-regulated the GRP78 mRNA expression level in the HC which suggests the involvement of unfolded protein response (UPR) in LPS-evoked behavioral anomalies. These results highlight the neuroprotective potential of SPB in LPS-induced anxiety and depressive illness model which may be partially due to inhibition of oxidative stress-neuroinflammatory cascade.

  18. Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E₂ receptor EP4

    Directory of Open Access Journals (Sweden)

    Yu Ah Hong

    2017-06-01

    Full Text Available Background: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS-induced renal proximal tubular cell injury through the prostaglandin E₂ (PGE₂ receptor EP4. Methods: Human renal tubular epithelial (HK-2 cells were pretreated with paricalcitol (2 ng/mL for 1 hour and exposed to LPS (1 μg/mL. The effects of paricalcitol pretreatment in relation to an EP4 blockade using AH-23848 or EP4 small interfering RNA (siRNA were investigated. Results: The expression of cyclooxygenase-2, PGE₂, and EP4 were significantly increased in LPS-exposed HK-2 cells treated with paricalcitol compared with cells exposed to LPS only. Paricalcitol prevented cell death induced by LPS exposure, and the cotreatment of AH-23848 or EP4 siRNA offset these cell-protective effects. The phosphorylation and nuclear translocation of p65 nuclear factor-kappaB (NF-κB were decreased and the phosphorylation of Akt was increased in LPS-exposed cells with paricalcitol treatment. AH-23848 or EP4 siRNA inhibited the suppressive effects of paricalcitol on p65 NF-κB nuclear translocation and the activation of Akt. The production of proinflammatory cytokines and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were attenuated by paricalcitol in LPS exposed HK-2 cells. The cotreatment with an EP4 antagonist abolished these anti-inflammatory and antiapoptotic effects. Conclusion: EP4 plays a pivotal role in anti-inflammatory and antiapoptotic effects through Akt and NF-κB signaling after paricalcitol pretreatment in LPS-induced renal proximal tubule cell injury.

  19. Tanreqing Injection Attenuates Lipopolysaccharide-Induced Airway Inflammation through MAPK/NF-κB Signaling Pathways in Rats Model

    Science.gov (United States)

    Liu, Wei; Jiang, Hong-li; Cai, Lin-li; Yan, Min; Dong, Shou-jin; Mao, Bing

    2016-01-01

    Background. Tanreqing injection (TRQ) is a commonly used herbal patent medicine for treating inflammatory airway diseases in view of its outstanding anti-inflammatory properties. In this study, we explored the signaling pathways involved in contributions of TRQ to LPS-induced airway inflammation in rats. Methods/Design. Adult male Sprague Dawley (SD) rats randomly divided into different groups received intratracheal instillation of LPS and/or intraperitoneal injection of TRQ. Bronchoalveolar Lavage Fluid (BALF) and lung samples were collected at 24 h, 48 h, and 96 h after TRQ administration. Protein and mRNA levels of tumor necrosis factor- (TNF-) α, Interleukin- (IL-) 1β, IL-6, and IL-8 in BALF and lung homogenate were observed by ELISA and real-time PCR, respectively. Lung sections were stained for p38 MAPK and NF-κB detection by immunohistochemistry. Phospho-p38 MAPK, phosphor-extracellular signal-regulated kinases ERK1/2, phospho-SAPK/JNK, phospho-NF-κB p65, phospho-IKKα/β, and phospho-IκB-α were measured by western blot analysis. Results. The results showed that TRQ significantly counteracted LPS-stimulated release of TNF-α, IL-1β, IL-6, and IL-8, attenuated cells influx in BALF, mitigated mucus hypersecretion, suppressed phosphorylation of NF-κB p65, IκB-α, ΙKKα/β, ERK1/2, JNK, and p38 MAPK, and inhibited p38 MAPK and NF-κB p65 expression in rat lungs. Conclusions. Results of the current research indicate that TRQ possesses potent exhibitory effects in LPS-induced airway inflammation by, at least partially, suppressing the MAPKs and NF-κB signaling pathways, in a general dose-dependent manner. PMID:27366191

  20. Curcumin Attenuates Lipopolysaccharide-Induced Hepatic Lipid Metabolism Disorder by Modification of m6 A RNA Methylation in Piglets.

    Science.gov (United States)

    Lu, Na; Li, Xingmei; Yu, Jiayao; Li, Yi; Wang, Chao; Zhang, Lili; Wang, Tian; Zhong, Xiang

    2018-01-01

    N 6 -methyladenosine (m 6 A) regulates gene expression and affects cellular metabolism. In this study, we checked whether the regulation of lipid metabolism by curcumin is associated with m 6 A RNA methylation. We investigated the effects of dietary curcumin supplementation on lipopolysaccharide (LPS)-induced liver injury and lipid metabolism disorder, and on m 6 A RNA methylation in weaned piglets. A total of 24 Duroc × Large White × Landrace piglets were randomly assigned to control, LPS, and CurL (LPS challenge and 200 mg/kg dietary curcumin) groups (n = 8/group). The results showed that curcumin reduced the increase in relative liver weight as well as the concentrations of aspartate aminotransferase and lactate dehydrogenase induced by LPS injection in the plasma and liver of weaning piglets (p < 0.05). The amounts of total cholesterol and triacylglycerols were decreased by curcumin compared to that by the LPS injection (p < 0.05). Additionally, curcumin reduced the expression of Bcl-2 and Bax mRNA, whereas it increased the p53 mRNA level in the liver (p < 0.05). Curcumin inhibited the enhancement of SREBP-1c and SCD-1 mRNA levels induced by LPS in the liver. Notably, dietary curcumin affected the expression of METTL3, METTL14, ALKBH5, FTO, and YTHDF2 mRNA, and increased the abundance of m 6 A in the liver of piglets. In conclusion, the protective effect of curcumin in LPS-induced liver injury and hepatic lipid metabolism disruption might be due to the increase in m 6 A RNA methylation. Our study provides mechanistic insights into the effect of curcumin in protecting against hepatic injury during inflammation and metabolic diseases. © 2018 AOCS.

  1. Zinc supplementation during pregnancy protects against lipopolysaccharide-induced fetal growth restriction and demise through its anti-inflammatory effect.

    Science.gov (United States)

    Chen, Yuan-Hua; Zhao, Mei; Chen, Xue; Zhang, Ying; Wang, Hua; Huang, Ying-Ying; Wang, Zhen; Zhang, Zhi-Hui; Zhang, Cheng; Xu, De-Xiang

    2012-07-01

    LPS is associated with adverse developmental outcomes, including preterm delivery, fetal death, teratogenicity, and intrauterine growth restriction (IUGR). Previous reports showed that zinc protected against LPS-induced teratogenicity. In the current study, we investigated the effects of zinc supplementation during pregnancy on LPS-induced preterm delivery, fetal death and IUGR. All pregnant mice except controls were i.p. injected with LPS (75 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were administered zinc sulfate through drinking water (75 mg elemental Zn per liter) throughout the pregnancy. As expected, an i.p. injection with LPS daily from GD15 to GD17 resulted in 36.4% (4/11) of dams delivered before GD18. In dams that completed the pregnancy, 63.2% of fetuses were dead. Moreover, LPS significantly reduced fetal weight and crown-rump length. Of interest, zinc supplementation during pregnancy protected mice from LPS-induced preterm delivery and fetal death. In addition, zinc supplementation significantly alleviated LPS-induced IUGR and skeletal development retardation. Further experiments showed that zinc supplementation significantly attenuated LPS-induced expression of placental inflammatory cytokines and cyclooxygenase-2. Zinc supplementation also significantly attenuated LPS-induced activation of NF-κB and MAPK signaling in mononuclear sinusoidal trophoblast giant cells of the labyrinth zone. It inhibited LPS-induced placental AKT phosphorylation as well. In conclusion, zinc supplementation during pregnancy protects against LPS-induced fetal growth restriction and demise through its anti-inflammatory effect.

  2. Effect of penehyclidine hydrochloride on β-arrestin-1 expression in lipopolysaccharide-induced human pulmonary microvascular endothelial cells

    International Nuclear Information System (INIS)

    Zhan, J.; Xiao, F.; Zhang, Z.Z.; Wang, Y.P.; Chen, K.; Wang, Y.L.

    2013-01-01

    β-arrestins are expressed proteins that were first described, and are well-known, as negative regulators of G protein-coupled receptor signaling. Penehyclidine hydrochloride (PHC) is a new anti-cholinergic drug that can inhibit biomembrane lipid peroxidation, and decrease cytokines and oxyradicals. However, to date, no reports on the effects of PHC on β-arrestin-1 in cells have been published. The aim of this study was to investigate the effect of PHC on β-arrestin-1 expression in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMEC). Cultured HPMEC were pretreated with PHC, followed by LPS treatment. Muscarinic receptor mRNAs were assayed by real-time quantitative PCR. Cell viability was assayed by the methyl thiazolyl tetrazolium (MTT) conversion test. The dose and time effects of PHC on β-arrestin-1 expression in LPS-induced HPMEC were determined by Western blot analysis. Cell malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured. It was found that the M 3 receptor was the one most highly expressed, and was activated 5 min after LPS challenge. Furthermore, 2 μg/mL PHC significantly upregulated expression of β-arrestin-1 within 10 to 15 min. Compared with the control group, MDA levels in cells were remarkably increased and SOD activities were significantly decreased in LPS pretreated cells, while PHC markedly decreased MDA levels and increased SOD activities. We conclude that PHC attenuated ROS injury by upregulating β-arrestin-1 expression, thereby implicating a mechanism by which PHC may exert its protective effects against LPS-induced pulmonary microvascular endothelial cell injury

  3. Activation of the NLRP3 inflammasome in lipopolysaccharide-induced mouse fatigue and its relevance to chronic fatigue syndrome.

    Science.gov (United States)

    Zhang, Zi-Teng; Du, Xiu-Ming; Ma, Xiu-Juan; Zong, Ying; Chen, Ji-Kuai; Yu, Chen-Lin; Liu, Yan-Gang; Chen, Yong-Chun; Zhao, Li-Jun; Lu, Guo-Cai

    2016-04-05

    not significantly altered. These findings suggest that LPS-induced fatigue is an IL-1β-dependent process and that the NLRP3/caspase-1 pathway is involved in the mechanisms of LPS-induced fatigue behaviours. NLRP3/caspase-1 inhibition may be a promising therapy for fatigue treatment.

  4. Agmatine ameliorates lipopolysaccharide induced depressive-like behaviour in mice by targeting the underlying inflammatory and oxido-nitrosative mediators.

    Science.gov (United States)

    Gawali, Nitin B; Bulani, Vipin D; Chowdhury, Amrita A; Deshpande, Padmini S; Nagmoti, Dnyaneshwar M; Juvekar, Archana R

    2016-10-01

    Experimental and clinical evidence indicates that pro-inflammatory cytokines, oxidative stress and brain-derived neurotrophic factor (BDNF) signalling mechanisms play a role in the pathophysiology of depression. Agmatine is a neurotransmitter and/or neuromodulator that has emerged as a potential agent to manage diverse central nervous system disorders. Agmatine has been shown to exert antidepressant-like effect. The present study investigated ability of agmatine to abolish the depressive-like behaviour induced by the administration of the lipopolysaccharide (LPS) in mice. Agmatine (20 and 40mg/kg) was administered daily for 7days, then the mice were challenged with saline or LPS (0.83mg/kg; i.p.) on the 7th day. After 24h of LPS administration we tested mice for depressive-like behaviour. LPS treated animals presented an increase in immobility time in the forced-swim test (FST), tail suspension test (TST) which was reversed by agmatine pre-treatment (20 and 40mg/kg). Oxidative/nitrosative stress evoked by LPS was ameliorated by both doses of agmatine in hippocampus (HC) and prefrontal cortex (PFC). Administration of LPS caused an increase in interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), whereas BDNF was down regulated in the HC. Agmatine pre-treatment at 40mg/kg ameliorated LPS-induced neuroinflammation by attenuating brain IL-1β and TNF-α level. In addition, agmatine pre-treatment also up-regulated the BDNF level in the HC. The present study shows that pre-treatment of agmatine is able to abolish the behavioural responses in the FST and TST elicited by the LPS-induced model of depression that may depend on the inhibition of pro-inflammatory mediators, reduction of oxidative stress as well as activation neuroplasticity-related signalling in mice, suggesting that agmatine may constitute an monotherapy/adjuvant for the management of depression associated with inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Slit2 ameliorates renal inflammation and fibrosis after hypoxia-and lipopolysaccharide-induced epithelial cells injury in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xiangjun [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Yao, Qisheng, E-mail: yymcyqs@126.com [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Sun, Xinbo; Gong, Xiaoxin; Yang, Yong; Chen, Congbo [Department of Urology, Taihe Hospital, Hubei University of Medicine, Hubei (China); Shan, Guang [Department of Urology, Renmin Hospital of Wuhan University, Hubei (China)

    2017-03-01

    Hypoxic acute kidney injury (AKI) is often incompletely repaired and leads to chronic kidney disease (CKD), which is characterized by tubulointerstitial inflammation and fibrosis. The Slit2 family of secreted glycoproteins is expressed in the kidney, it has been shown to exert an anti-inflammatory activity and prevent ischemic renal injury in vivo. However, whether Slit2 reduces renal fibrosis and inflammation after hypoxic and inflammatory epithelial cells injury in vitro remains unknown. In this study, we aimed to evaluate whether Slit2 ameliorated fibrosis and inflammation in two renal epithelial cells line challenged with hypoxia and lipopolysaccharide (LPS). Renal epithelial cells were treated with hypoxia and LPS to induce cell injury. Hoechst staining and Western blot analysis was conducted to examine epithelial cells injury. Immunofluorescence staining and Western blot analysis was performed to evaluate tubulointerstitial fibrosis. Real-time polymerase chain reaction (PCR) tested the inflammatory factor interleukin (IL)−1β and tumor necrosis factor (TNF)-α, and Western blot analysis determined the hypoxia-inducible factor (HIF)−1α, Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB. Results revealed that hypoxia induced epithelial cells apoptosis, inflammatory factor IL-1β and TNF-α release and tubulointerstitial fibrosis. LPS could exacerbate hypoxia -induced epithelial cells apoptosis, IL-1β and TNF-α release and fibrosis. Slit2 reduced the expression of fibronectin, the rate of epithelial cell apoptosis, and the expression of inflammatory factor. Slit2 could also inhibit the expression of TLR4 and NF-κB, but not the expression of HIF-1α. Therefore, Slit2 attenuated inflammation and fibrosis after LPS- and hypoxia-induced epithelial cells injury via the TLR4/NF-κB signaling pathway, but not depending on the HIF-1α signaling pathway. - Highlights: • Slit2 ameliorates inflammation after hypoxia-and LPS-induced epithelial cells injury

  6. Effect of caffeic acid phenethyl ester on Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    Science.gov (United States)

    Choi, E-Y; Choe, S-H; Hyeon, J-Y; Choi, J-I; Choi, I S; Kim, S-J

    2015-12-01

    Caffeic acid phenethyl ester (CAPE) has numerous potentially beneficial properties, including antioxidant, immunomodulatory and anti-inflammatory activities. However, the effect of CAPE on periodontal disease has not been studied before. This study was designed to investigate the efficacy of CAPE in ameliorating the production of proinflammatory mediators in macrophages activated by lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in periodontal disease. LPS from P. intermedia ATCC 25611 was isolated by using the standard hot phenol-water method. Culture supernatants were assayed for nitric oxide (NO), interleukin (IL)-1β and IL-6. We used real-time polymerase chain reaction to quantify inducible NO synthase, IL-1β, IL-6, heme oxygenase (HO)-1 and suppressors of cytokine signaling (SOCS) 1 mRNA expression. HO-1 protein expression and levels of signaling proteins were assessed by immunoblot analysis. DNA-binding activities of NF-κB subunits were analyzed by using the enzyme-linked immunosorbent assay-based kits. CAPE exerted significant inhibitory effects on P. intermedia LPS-induced production of NO, IL-1β and IL-6 as well as their mRNA expression in RAW264.7 cells. CAPE-induced HO-1 expression in cells activated with P. intermedia LPS, and selective inhibition of HO-1 activity by tin protoporphyrin IX attenuated the inhibitory effect of CAPE on LPS-induced NO production. CAPE did not interfere with IκB-α degradation induced by P. intermedia LPS. Instead, CAPE decreased nuclear translocation of NF-κB p65 and p50 subunits induced with LPS, and lessened LPS-induced p50 binding activity. Further, CAPE showed strong inhibitory effects on LPS-induced signal transducer and activator of transcription 1 and 3 phosphorylation. Besides, CAPE significantly elevated SOCS1 mRNA expression in P. intermedia LPS-stimulated cells. Modulation of host response by CAPE may represent an attractive strategy towards the treatment of periodontal disease

  7. Eugenol stimulates lactate accumulation yet inhibits volatile fatty acid production and eliminates coliform bacteria in cattle and swine waste.

    Science.gov (United States)

    Varel, V H; Miller, D L

    2004-01-01

    To determine how eugenol affects fermentation parameters and faecal coliforms in cattle and swine waste slurries stored anaerobically. Waste slurries (faeces:urine:water, 50:35:15) were blended with and without additives and aliquoted to triplicate 1-l flasks. Faecal coliforms were eliminated in cattle and swine waste slurries within 1 or 2 days with additions of eugenol at 10.05 mm (0.15%) and 16.75 mm (0.25%). At these concentrations volatile fatty acids (VFA) were reduced ca 70 and 50% in cattle and swine waste, respectively, over 6-8 weeks. Additionally, in cattle waste, eugenol stimulated the accumulation of lactate (>180 mm) when compared with thymol treatment (20 mm lactate). In swine waste, lactate accumulation did not occur without additives; eugenol and thymol stimulated lactate accumulation to concentrations of 22 and 32 mm, respectively. Eugenol added to cattle waste may be more beneficial than thymol because not only does it effectively control faecal coliforms and odour (VFA production), it also stimulates lactate accumulation. This in turn, causes the pH to drop more rapidly, further inhibiting microbial activity and nutrient emissions. Plant essential oils have the potential to solve some of the environmental problems associated with consolidated animal feeding operations. Thymol and eugenol reduce fermentative activity, thus, have the potential to reduce emissions of greenhouse gases and odour, and curtail transmission of pathogens in cattle and swine wastes.

  8. Inhibition of acid mine drainage and immobilization of heavy metals from copper flotation tailings using a marble cutting waste

    Science.gov (United States)

    Tozsin, Gulsen

    2016-01-01

    Acid mine drainage (AMD) with high concentrations of sulfates and metals is generated by the oxidation of sulfide bearing wastes. CaCO3-rich marble cutting waste is a residual material produced by the cutting and polishing of marble stone. In this study, the feasibility of using the marble cutting waste as an acid-neutralizing agent to inhibit AMD and immobilize heavy metals from copper flotation tailings (sulfide- bearing wastes) was investigated. Continuous-stirring shake-flask tests were conducted for 40 d, and the pH value, sulfate content, and dissolved metal content of the leachate were analyzed every 10 d to determine the effectiveness of the marble cutting waste as an acid neutralizer. For comparison, CaCO3 was also used as a neutralizing agent. The average pH value of the leachate was 2.1 at the beginning of the experiment ( t = 0). In the experiment employing the marble cutting waste, the pH value of the leachate changed from 6.5 to 7.8, and the sulfate and iron concentrations decreased from 4558 to 838 mg/L and from 536 to 0.01 mg/L, respectively, after 40 d. The marble cutting waste also removed more than 80wt% of heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn) from AMD generated by copper flotation tailings.

  9. Sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation will increase in lipopolysaccharide-induced inflammation in vitro model.

    Science.gov (United States)

    Zuo, Wen-Qi; Hu, Yu-Juan; Yang, Yang; Zhao, Xue-Yan; Zhang, Yuan-Yuan; Kong, Wen; Kong, Wei-Jia

    2015-05-29

    .0 W/kg when cells are in fragile or micro-damaged condition. It seems that the sensitivity of SGN to damage caused by mobile phone electromagnetic radiation will increase in a lipopolysaccharide-induced inflammation in vitro model.

  10. Molecular evidence for the existence of lipopolysaccharide-induced TNF-alpha factor (LITAF) and Rel/NF-kB pathways in disk abalone (Haliotis discus discus).

    Science.gov (United States)

    De Zoysa, Mahanama; Nikapitiya, Chamilani; Oh, Chulhong; Whang, Ilson; Lee, Jae-Seong; Jung, Sung-Ju; Choi, Cheol Young; Lee, Jehee

    2010-01-01

    The lipopolysaccharide-induced TNF-alpha factor (LITAF) and Rel family nuclear factor kappaB (Rel/NF-kB) are two important transcription factors which play major roles in the regulating inflammatory cytokine, apoptosis and immune related genes. Here, we report the discovery of disk abalone LITAF (AbLITAF) and Rel/NF-kB (AbRel/NF-kB) homologues and their immune responses. Full-length cDNA of AbLITAF consists of 441 bp open reading frame (ORF) that translates into putative peptide of 147 aa. Analysis of AbLITAF sequence showed it has characteristic LITAF (Zn(+2)) binding domain with two CXXC motifs. Phylogenetic analysis results further revealed that AbLITAF is a member of LITAF family. AbRel/NF-kB is 584 aa protein that contains several characteristic motifs including Rel homology domain (RHD), Rel protein signature, DNA binding motif, nuclear localization signal (NLS) and transcription factor immunoglobulin - like fold (TIG) similar to their invertebrate and vertebrate counterparts. Tissue specific analysis results showed that both AbLITAF and AbRel/NF-kB mRNA was expressed ubiquitously in all selected tissues in constitutive manner. However, constitutive expression of AbLITAF was higher than AbRel/NF-kB in all tissues except mantle. Upon immune challenge by bacteria (Vibrio alginolyticus, Vibrio parahemolyticus and Lysteria monocytogenes) and viral hemoragic septicemia virus (VHSV), AbLITAF showed the significant up-regulation in gills while AbRel/NF-kB transcription was not change significantly. Based on transcriptional response against immune challenge, we could suggest that regulation of TNF-alpha expression may have occurred mainly by LITAF activation rather than NF-kB in disk abalone. The cumulative data from other molluscs and our data with reference to TNF-alpha, LITAF and Rel/NF-kB from disk abalone provide strong evidence that LITAF and NF-kB are independent pathways likely to occur throughout the Phylum mollusca. 2010 Elsevier Ltd. All rights reserved.

  11. Modeling of anaerobic degradation of solid slaughterhouse waste: inhibition effects of long-chain fatty acids or ammonia.

    Science.gov (United States)

    Lokshina, L Y; Vavilin, V A; Salminen, E; Rintala, J

    2003-01-01

    The anaerobic bioconversion of solid poultry slaughterhouse wastes was kinetically investigated. The modified version of simulation model was applied for description of experimental data in mesophilic laboratory digester and assays. Additionally, stages of formation and consumption of long chain fatty acids (LCFA) were included in the model. Batch data on volatile solids, ammonium, acetate, butyrate, propionate, LCFA concentrations, pH level, cumulative volume, and methane partial pressure were used for model calibration. As a reference, the model was used to describe digestion of solid sorted household waste. Simulation results showed that an inhibition of polymer hydrolysis by volatile fatty acids and acetogenesis by NH3 or LCFA could be responsible for the complex system dynamics during degradation of lipid- and protein-rich wastes.

  12. Pantoprazole blocks the JAK2/STAT3 pathway to alleviate skeletal muscle wasting in cancer cachexia by inhibiting inflammatory response.

    Science.gov (United States)

    Guo, Dunwei; Wang, Chaoyi; Wang, Qiang; Qiao, Zhongpeng; Tang, Hua

    2017-06-13

    Cancer cachexia is often present in patients with advanced malignant tumors, and the subsequent body weight reduction results in poor quality of life. However, there has been no progress in developing effective clinical therapeutic strategies for skeletal muscle wasting in cancer cachexia. Herein, we explored the functions of pantoprazole on cancer cachexia skeletal muscle wasting. The mouse colon adenocarcinoma cell line C26 was inoculated in the right forelimb of male BALB/C mice to establish a cancer cachexia model. The animals were treated with or without different concentrations of pantoprazole orally, and the body weight, tumor growth, spontaneous activity, and muscle functions were determined at various time points. Two weeks later, the levels of serum IL-6 and TNF-α, the mRNA levels of gastrocnemius JAK2 and STAT3, and the expression levels of p-JAK2, p-STAT3, Fbx32, and MuRF1 were examined with ELISA assay, qRT-PCR assay, and Western blotting, respectively. Further studies were performed to assess the levels of Fbx32 and MuRF1 expression and morphological changes. Pantoprazole can alleviate cancer cachexia-induced body weight reduction and inhibit skeletal muscle wasting in a dose-dependent manner. Our results indicated that pantoprazole treatment can decrease the levels of serum IL-6 and TNF-α (56.3% and 67.6%, respectively), and inhibit the activation of the JAK2/STAT3 signaling pathway. Moreover, the expression levels of MuRF1 and Fbx32 were also suppressed after pantoprazole treatment. Our findings suggested that pantoprazole can alleviate cancer cachexia skeletal muscle wasting by inhibiting the inflammatory response and blocking the JAK2/STAT3 or ubiquitin proteasome pathway.

  13. Valproic acid attenuates skeletal muscle wasting by inhibiting C/EBPβ-regulated atrogin1 expression in cancer cachexia.

    Science.gov (United States)

    Sun, Rulin; Zhang, Santao; Hu, Wenjun; Lu, Xing; Lou, Ning; Yang, Zhende; Chen, Shaoyong; Zhang, Xiaoping; Yang, Hongmei

    2016-07-01

    Muscle wasting is the hallmark of cancer cachexia and is associated with poor quality of life and increased mortality. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has important biological effects in the treatment of muscular dystrophy. To verify whether VPA could ameliorate muscle wasting induced by cancer cachexia, we explored the role of VPA in two cancer cachectic mouse models [induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC)] and atrophied C2C12 myotubes [induced by C26 cell conditioned medium (CCM) or LLC cell conditioned medium (LCM)]. Our data demonstrated that treatment with VPA increased the mass and cross-sectional area of skeletal muscles in tumor-bearing mice. Furthermore, treatment with VPA also increased the diameter of myotubes cultured in conditioned medium. The skeletal muscles in cachectic mice or atrophied myotubes treated with VPA exhibited reduced levels of CCAAT/enhancer binding protein beta (C/EBPβ), resulting in atrogin1 downregulation and the eventual alleviation of muscle wasting and myotube atrophy. Moreover, atrogin1 promoter activity in myotubes was stimulated by CCM via activating the C/EBPβ-responsive cis-element and subsequently inhibited by VPA. In contrast to the effect of VPA on the levels of C/EBPβ, the levels of inactivating forkhead box O3 (FoxO3a) were unaffected. In summary, VPA attenuated muscle wasting and myotube atrophy and reduced C/EBPβ binding to atrogin1 promoter locus in the myotubes. Our discoveries indicate that HDAC inhibition by VPA might be a promising new approach for the preservation of skeletal muscle in cancer cachexia. Copyright © 2016 the American Physiological Society.

  14. Bacterial lipopolysaccharide-induced systemic inflammation alters perfusion of white matter-rich regions without altering flow in brain-irrigating arteries: Relationship to blood-brain barrier breakdown?

    Science.gov (United States)

    Dhaya, Ibtihel; Griton, Marion; Raffard, Gérard; Amri, Mohamed; Hiba, Bassem; Konsman, Jan Pieter

    2018-01-15

    To better understand brain dysfunction during sepsis, cerebral arterial blood flow was assessed with Phase Contrast Magnetic Resonance Imaging, perfusion with Arterial Spin Labeling and structure with diffusion-weighted Magnetic Resonance Imaging in rats after intraperitoneal administration of bacterial lipopolysaccharides. Although cerebral arterial flow was not altered, perfusion of the corpus callosum region and diffusion parallel to its fibers were higher after lipopolysaccharide administration as compared to saline injection. In parallel, lipopolysaccharide induced perivascular immunoglobulin-immunoreactivity in white matter. These findings indicate that systemic inflammation can result in increased perfusion, blood-brain barrier breakdown and altered water diffusion in white matter. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Inhibition of nitrate stress corrosion cracking of mild steel in nuclear process wastes

    International Nuclear Information System (INIS)

    Donovan, J.A.

    1975-01-01

    The concentration of hydroxide and nitrite ions necessary to prevent crack growth in A-285-B steel exposed to waste solutions was determined by the systematic testing of solutions within the ranges of hydroxide, nitrate, and nitrite concentrations found in waste tanks. The relative susceptibility to SCC was assumed to be dependent on the concentrations of nitrate, nitrite, and hydroxyl ions; the other components were assumed to have little effect on cracking. All of the tests were done at 97 0 C, with specimens loaded initially to an effective stress intensity of 45 ksi √in. Both the temperature of exposure and the initial stress intensity create conditions more severe than would normally be found in the waste tanks. All specimens were exposed for a minimum of 1000 hours. Results showed that the aggressiveness of the solutions increased with increasing nitrate ion concentration. For example, cracks grew in 5M NO 3 - + 0.3M NO 2 - , but not in 1.5M NO 3 - + 0.3M NO 2 - . Also, the solutions causing crack growth within the range of compositions found in the waste tank were concentrated in the high nitrate--low nitrite, hydroxyl ion region. Most of the results were obtained with solutions containing 5M NO 3 - and various amounts of nitrite and hydroxyl ion concentrations. (U.S.)

  16. Effects of acteoside on lipopolysaccharide-induced inflammation in acute lung injury via regulation of NF-κB pathway in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Jing, Wang; Chunhua, Ma, E-mail: machunhuabest@126.com; Shumin, Wang, E-mail: wangshuminch@126.com

    2015-06-01

    The purpose of the present study was to investigate the protective role of acteoside (AC) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). BalB/c mice intraperitoneally received AC (30, and 60 mg/kg) or dexamethasone (2 mg/kg) 2 h prior to or after intratracheal instillation of LPS. Treatment with AC significantly decreased lung wet-to-dry weight (W/D) ratio and lung myeloperoxidase (MPO) activity and ameliorated LPS-induced lung histopathological changes. In addition, AC increased super oxide dismutase (SOD) level and inhibited malondialdehyde (MDA) content, total cell and neutrophil infiltrations, and levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) in LPS-stimulated mice. Furthermore, we demonstrated that AC inhibited the phosphorylation of IκBα, nuclear factor-κB (NF-κB) p65, inhibitor of nuclear factor kappa-B kinase-α (IKK-α) and inhibitor of nuclear factor kappa-B kinase-β (IKKβ) in LPS-induced inflammation in A549 cells. Our data suggested that LPS evoked the inflammatory response in lung epithelial cells A549. The experimental results indicated that the protective mechanism of AC might be attributed partly to the inhibition of proinflammatory cytokine production and NF-κB activation. - Highlights: • Acteoside inhibited inflammation in LPS-induced lung injury in mice. • Acteoside inhibited inflammation in lung epithelial cells A549. • Acteoside inhibited NF-kB activation in LPS-induced mice and lung epithelial cells A549.

  17. The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Mikkelsen, Jens D

    2012-01-01

    The anti-inflammatory properties of, particularly the α7, nicotinic acetylcholine receptors (nAChRs) in the peripheral immune system are well documented. There are also reports of anti-inflammatory actions of nicotine in the CNS, but it is unclear, whether this is due to activation or inhibition...

  18. Preventative effect of OMZ-SPT on lipopolysaccharide-induced acute lung injury and inflammation via nuclear factor-kappa B signaling in mice

    International Nuclear Information System (INIS)

    Wang, Ting; Hou, Wanru; Fu, Zhou

    2017-01-01

    Acute lung injury (ALI) is an early pathophysiologic change in acute respiratory distress syndrome and its management can be challenging. Omalizumab (Xolair™) is a recombinant DNA-derived, humanized antibody. OMZ-SPT is a polypeptide on the heavy chain of omalizumab monoclonal antibody. Here, we found that intramuscular administration of OMZ-SPT significantly improved survival and attenuated lung inflammation in female C57BL/6 mice suffering from lipopolysaccharide (LPS)-induced ALI. We also demonstrated that OMZ-SPT can inhibit expression of the inflammatory cytokines tumor necrosis factor-α, interleukin-1β and interleukin-6 by ELISA in mice suffering from LPS-induced ALI and a mouse macrophage line (RAW264.7 cells). In addition, we showed that OMZ-SPT inhibited LPS-induced activation of nuclear factor-kappa B (NF-κB) signaling and total expression of NF-κB by western blotting. These data suggest that OMZ-SPT could be a novel therapeutic choice for ALI. - Highlights: • OMZ-SPT is a polypeptide on the heavy chain of omalizumab monoclonal antibody. • Omalizumab (Xolair™) have anti-inflammatory effects. • OMZ-SPT can inhibit inflammatory responses and lung injury in LPS-induced ALI mice. • Protective effect of OMZ-SPT on ALI is due to inhibition of NF-κB signaling. • OMZ-SPT could be a novel therapeutic choice for ALI.

  19. Ulinastatin suppresses lipopolysaccharide induced neuro-inflammation through the downregulation of nuclear factor-κB in SD rat hippocampal astrocyte

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuting; Zhao, Lei; Fu, Huiqun [Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, 100053 Beijing (China); Wu, Yan [Department of Anatomy, Capital Medical University, 100069 Beijing (China); Wang, Tianlong, E-mail: litingliting258@163.com [Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, 100053 Beijing (China)

    2015-03-20

    Astrocyte activation plays a pivotal role in neuroinflammation, which contributes to neuronal damage, so the inhibition of astrocyte activation may alleviate the progression of neurodegeneration. Recent studies have proved that urinary trypsin inhibitor ulinastatin could inhibit NF-kB activation. In our study, the inhibitory effects of ulinastatin on the production of pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-reduced primary astrocyte. Our results showed that ulinastatin significantly inhibited LPS-induced astrogliosis, which is measured by MTT and BrdU. Ulinastatin decreased the production of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1β, it significantly decreased both the mRNA and the protein levels of these pro-inflammatory cytokines and also increased the protein levels of IκB-α binded to NF-κB, which blocked NF-κB translocation to the nucleus and prevented its activity. Our results suggest that ulinastatin is able to inhibit neuroinflammation by interfering with NF-κB signaling. The study provides direct evidence of potential therapy methods of ulinastatin for the treatment of neuroinflammatory diseases. - Highlights: • The anti-inflammatory effect of UTI on hippocampal astrocyte. • UTI showed protective effect on neuroinflammation by the downregulation of NF-κB. • UTI led to expression of cytokines decreased in concentration and time dependence.

  20. Ulinastatin suppresses lipopolysaccharide induced neuro-inflammation through the downregulation of nuclear factor-κB in SD rat hippocampal astrocyte

    International Nuclear Information System (INIS)

    Li, Yuting; Zhao, Lei; Fu, Huiqun; Wu, Yan; Wang, Tianlong

    2015-01-01

    Astrocyte activation plays a pivotal role in neuroinflammation, which contributes to neuronal damage, so the inhibition of astrocyte activation may alleviate the progression of neurodegeneration. Recent studies have proved that urinary trypsin inhibitor ulinastatin could inhibit NF-kB activation. In our study, the inhibitory effects of ulinastatin on the production of pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-reduced primary astrocyte. Our results showed that ulinastatin significantly inhibited LPS-induced astrogliosis, which is measured by MTT and BrdU. Ulinastatin decreased the production of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1β, it significantly decreased both the mRNA and the protein levels of these pro-inflammatory cytokines and also increased the protein levels of IκB-α binded to NF-κB, which blocked NF-κB translocation to the nucleus and prevented its activity. Our results suggest that ulinastatin is able to inhibit neuroinflammation by interfering with NF-κB signaling. The study provides direct evidence of potential therapy methods of ulinastatin for the treatment of neuroinflammatory diseases. - Highlights: • The anti-inflammatory effect of UTI on hippocampal astrocyte. • UTI showed protective effect on neuroinflammation by the downregulation of NF-κB. • UTI led to expression of cytokines decreased in concentration and time dependence

  1. Muscle wasting and impaired myogenesis in tumor bearing mice are prevented by ERK inhibition.

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    Fabio Penna

    Full Text Available BACKGROUND: The onset of cachexia is a frequent feature in cancer patients. Prominent characteristic of this syndrome is the loss of body and muscle weight, this latter being mainly supported by increased protein breakdown rates. While the signaling pathways dependent on IGF-1 or myostatin were causally involved in muscle atrophy, the role of the Mitogen-Activated-Protein-Kinases is still largely debated. The present study investigated this point on mice bearing the C26 colon adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: C26-bearing mice display a marked loss of body weight and muscle mass, this latter associated with increased phosphorylated (p-ERK. Administration of the ERK inhibitor PD98059 to tumor bearers attenuates muscle depletion and weakness, while restoring normal atrogin-1 expression. In C26 hosts, muscle wasting is also associated with increased Pax7 expression and reduced myogenin levels. Such pattern, suggestive of impaired myogenesis, is reversed by PD98059. Increased p-ERK and reduced myosin heavy chain content can be observed in TNFα-treated C2C12 myotubes, while decreased myogenin and MyoD levels occur in differentiating myoblasts exposed to the cytokine. All these changes are prevented by PD98059. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that ERK is involved in the pathogenesis of muscle wasting in cancer cachexia and could thus be proposed as a therapeutic target.

  2. Attenuation of prostaglandin E2 elimination across the mouse blood-brain barrier in lipopolysaccharide-induced inflammation and additive inhibitory effect of cefmetazole

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    Akanuma Shin-ichi

    2011-10-01

    Full Text Available Abstract Background Peripheral administration of lipopolysaccharide (LPS induces inflammation and increases cerebral prostaglandin E2 (PGE2 concentration. PGE2 is eliminated from brain across the blood-brain barrier (BBB in mice, and this process is inhibited by intracerebral or intravenous pre-administration of anti-inflammatory drugs and antibiotics such as cefmetazole and cefazolin that inhibit multidrug resistance-associated protein 4 (Mrp4/Abcc4-mediated PGE2 transport. The purpose of this study was to examine the effect of LPS-induced inflammation on PGE2 elimination from brain, and whether antibiotics further inhibit PGE2 elimination in LPS-treated mice. Methods [3H]PGE2 elimination across the BBB of intraperitoneally LPS-treated mice was assessed by the brain efflux index (BEI method. Transporter protein amounts in brain capillaries were quantified by liquid chromatography-tandem mass spectrometry. Results The apparent elimination rate of [3H]PGE2 from brain was lower by 87%, in LPS-treated mice compared with saline-treated mice. The Mrp4 protein amount was unchanged in brain capillaries of LPS-treated mice compared with saline-treated mice, while the protein amounts of organic anion transporter 3 (Oat3/Slc22a8 and organic anion transporting polypeptide 1a4 (Oatp1a4/Slco1a4 were decreased by 26% and 39%, respectively. Either intracerebral or intravenous pre-administration of cefmetazole further inhibited PGE2 elimination in LPS-treated mice. However, intracerebral or intravenous pre-administration of cefazolin had little effect on PGE2 elimination in LPS-treated mice, or in LPS-untreated mice given Oat3 and Oatp1a4 inhibitors. These results indicate that peripheral administration of cefmetazole inhibits PGE2 elimination across the BBB in LPS-treated mice. Conclusion PGE2 elimination across the BBB is attenuated in an LPS-induced mouse model of inflammation. Peripheral administration of cefmetazole further inhibits PGE2 elimination in LPS

  3. Alpinetin attenuates inflammatory responses by interfering toll-like receptor 4/nuclear factor kappa B signaling pathway in lipopolysaccharide-induced mastitis in mice.

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    Chen, Haijin; Mo, Xiaodong; Yu, Jinlong; Huang, Zonghai

    2013-09-01

    Alpinetin, a novel plant flavonoid derived from Alpinia katsumadai Hayata, has been reported to exhibit anti-inflammatory properties. However, the effect of alpinetin on mastitis has not been investigated. The aim of this study was to investigate the protective effect of alpinetin against lipopolysaccharide (LPS)-induced mastitis and to clarify the possible mechanism. In the present study, primary mouse mammary epithelial cells and an LPS-induced mouse mastitis model were used to investigate the effect of alpinetin on mastitis and the possible mechanism. In vivo, we observed that alpinetin significantly attenuated the infiltration of neutrophilic granulocytes, and the activation of myeloperoxidase; down-regulated the level of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6; inhibited the phosphorylation of IκB-α, NF-κB p65 and the expression of TLR4, caused by LPS. In vitro, we also observed that alpinetin inhibited the expression of TLR4 and the production of TNF-α, IL-1β and IL-6 in LPS-stimulated primary mouse mammary epithelial cells. However, alpinetin could not inhibit the production of IL-1β and IL-6 in TNF-α-stimulated primary mouse mammary epithelial cells. In conclusion, our results suggest that the anti-inflammatory effects of alpinetin against LPS-induced mastitis may be due to its ability to inhibit TLR4-mediated NF-κB signaling pathways. Alpinetin may be a promising potential therapeutic reagent for mastitis treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. The Anti-Inflammatory Effect of Human Telomerase-Derived Peptide on P. gingivalis Lipopolysaccharide-Induced Inflammatory Cytokine Production and Its Mechanism in Human Dental Pulp Cells

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    Yoo-Jin Ko

    2015-01-01

    Full Text Available Porphyromonas gingivalis is considered with inducing pulpal inflammation and has lipopolysaccharide (LPS as an inflammatory stimulator. GV1001 peptide has anticancer and anti-inflammation activity due to inhibiting activation of signaling molecules after penetration into the various types of cells. Therefore, this study examined inhibitory effect of GV1001 on dental pulp cells (hDPCs stimulated by P. gingivalis LPS. The intracellular distribution of GV1001 was analyzed by confocal microscopy. Real-time RT-PCR was performed to determine the expression levels of TNF-α and IL-6 cytokines. The role of signaling by MAP kinases (ERK and p38 was explored using Western blot analysis. The effect of GV1001 peptide on hDPCs viability was measured by MTT assay. GV1001 was predominantly located in hDPC cytoplasm. The peptide inhibited P. gingivalis LPS-induced TNF-α and IL-6 production in hDPCs without significant cytotoxicity. Furthermore, GV1001 treatment markedly inhibited the phosphorylation of MAP kinases (ERK and p38 in LPS-stimulated hDPCs. GV1001 may prevent P. gingivalis LPS-induced inflammation of apical tissue. Also, these findings provide mechanistic insight into how GV1001 peptide causes anti-inflammatory actions in LPS-stimulated pulpitis without significantly affecting cell viability.

  5. Anthocyanins Downregulate Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglial Cells by Suppressing the NF-κB and Akt/MAPKs Signaling Pathways

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    Yung Hyun Choi

    2013-01-01

    Full Text Available Anthocyanins are naturally occurring polyphenols that impart bright color to fruits, vegetables and plants and have a variety of protective properties, which have generally been attributed to their antioxidant capacity. However, little is known about the molecular mechanisms underlying anti-inflammatory effects of anthocyanins related to neurodegenerative diseases. Therefore, we determined whether anthocyanins isolated from black soybean seed coats would inhibit pro-inflammatory mediators and cytokines in lipopolysaccharide (LPS-stimulated murine BV2 microglial cells. Our results showed that anthocyanins significantly inhibited LPS-induced pro-inflammatory mediators, such as nitric oxide (NO and prostaglandin E2, and pro-inflammatory cytokines including tumor necrosis factor (TNF-α and interleukin (IL-1β, without significant cytotoxicity. Anthocyanins also downregulated excessive expression of inducible NO synthase, cyclooxygenase-2, TNF-α, and IL-1β in LPS-stimulated BV2 cells. Moreover, anthocyanins inhibited nuclear translocation of nuclear factor-kappa B (NF-κB by reducing inhibitor of NF-κB alpha degradation as well as phosphorylating extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and Akt. These findings suggest that anthocyanins may offer substantial therapeutic potential for treating inflammatory and neurodegenerative diseases accompanied by microglial activation.

  6. Suppressive Effect on Lipopolysaccharide-Induced Proinflammatory Mediators by Citrus aurantium L. in Macrophage RAW 264.7 Cells via NF-κB Signal Pathway

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    Sang-Rim Kang

    2011-01-01

    Full Text Available Citrus fruits have been used as an edible fruit and a traditional medicine since ancient times. In particular, the peels of immature citrus fruits are used widely in traditional herbal medicine in Korea, as they are believed to contain bioactive components exerting anti-inflammatory activity. This study examined whether the crude methanol extract of Citrus aurantium L. (CME has a suppressive effect on inducible enzymes and proinflammatory cytokines by inhibiting the NF-κB pathway in LPS-stimulated macrophage RAW 264.7 cells. The cells were pretreated with the indicated concentrations of CME (5, 10, 20, and 50 μg/mL and then treated with LPS (1 μg/mL. The results showed that CME (10, 20, and 50 μg/mL inhibited the LPS- (1 μg/mL induced mRNA and protein expression of iNOS in macrophage Raw 264.7 cells. In addition, the expression of COX-2 was inhibited at the mRNA and protein levels by CME in a dose-dependent manner. The mRNA expression of proinflammatory cytokines, such as TNF-α and IL-6, were markedly reduced by CME (10, 20, and 50 μg/mL. Moreover, CME clearly suppressed the nuclear translocation of the NF-κB p65 subunits, which was correlated with its inhibitory effect on I-κB phosphorylation. These results suggest that CME has anti-inflammatory properties by modulating the expression of COX-2, iNOS, and proinflammatory cytokines, such as TNF-α and IL-6, in macrophage RAW 264.7 cells via the NF-κB pathway.

  7. 5-Methoxyl Aesculetin Abrogates Lipopolysaccharide-Induced Inflammation by Suppressing MAPK and AP-1 Pathways in RAW 264.7 Cells

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    Lei Wu

    2016-03-01

    Full Text Available For the first time, a pale amorphous coumarin derivative, 5-methoxyl aesculetin (MOA, was isolated from the dried bark of Fraxinus rhynchophylla Hance (Oleaceae. MOA modulates cytokine expression in lipopolysaccharide (LPS-treated RAW 264.7 macrophages, but the precise mechanisms are still not fully understood. We determined the effects of MOA on the production of inflammatory mediators and pro-inflammatory cytokines in the LPS-induced inflammatory responses of RAW 264.7 macrophages. MOA significantly inhibited the LPS-induced production of nitric oxide (NO, prostaglandin E2 (PGE2, tumor necrosis factor-α (TNF-α, interleukin-6, and interleukin-1β. It also effectively attenuated inducible nitric oxide (NO synthase, cyclooxygenase-2, and TNF-α mRNA expression and significantly decreased the levels of intracellular reactive oxygen species. It inhibited phosphorylation of the extracellular signal-regulated kinase (ERK1/2, thus blocking nuclear translocation of activation protein (AP-1. In a molecular docking study, MOA was shown to target the binding site of ERK via the formation of three hydrogen bonds with two residues of the kinase, which is sufficient for the inhibition of ERK. These results suggest that the anti-inflammatory effects of MOA in RAW 264.7 macrophages derive from its ability to block both the activation of mitogen-activated protein kinases (MAPKs and one of their downstream transcription factors, activator protein-1 (AP-1. Our observations support the need for further research into MOA as a promising therapeutic agent in inflammatory diseases.

  8. 5-Methoxyl Aesculetin Abrogates Lipopolysaccharide-Induced Inflammation by Suppressing MAPK and AP-1 Pathways in RAW 264.7 Cells

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    Wu, Lei; Li, Xueqin; Wu, Haifeng; Long, Wei; Jiang, Xiaojian; Shen, Ting; Qiang, Qian; Si, Chuanling; Wang, Xinfeng; Jiang, Yunyao; Hu, Weicheng

    2016-01-01

    For the first time, a pale amorphous coumarin derivative, 5-methoxyl aesculetin (MOA), was isolated from the dried bark of Fraxinus rhynchophylla Hance (Oleaceae). MOA modulates cytokine expression in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, but the precise mechanisms are still not fully understood. We determined the effects of MOA on the production of inflammatory mediators and pro-inflammatory cytokines in the LPS-induced inflammatory responses of RAW 264.7 macrophages. MOA significantly inhibited the LPS-induced production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-1β. It also effectively attenuated inducible nitric oxide (NO) synthase, cyclooxygenase-2, and TNF-α mRNA expression and significantly decreased the levels of intracellular reactive oxygen species. It inhibited phosphorylation of the extracellular signal-regulated kinase (ERK1/2), thus blocking nuclear translocation of activation protein (AP)-1. In a molecular docking study, MOA was shown to target the binding site of ERK via the formation of three hydrogen bonds with two residues of the kinase, which is sufficient for the inhibition of ERK. These results suggest that the anti-inflammatory effects of MOA in RAW 264.7 macrophages derive from its ability to block both the activation of mitogen-activated protein kinases (MAPKs) and one of their downstream transcription factors, activator protein-1 (AP-1). Our observations support the need for further research into MOA as a promising therapeutic agent in inflammatory diseases. PMID:26938526

  9. Transcriptional profiles of Rel/NF-κB, inhibitor of NF-κB (IκB), and lipopolysaccharide-induced TNF-α factor (LITAF) in the lipopolysaccharide (LPS) and two Vibrio sp.-exposed intertidal copepod, Tigriopus japonicus.

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    Kim, Bo-Mi; Jeong, Chang-Bum; Rhee, Jae-Sung; Lee, Jae-Seong

    2014-02-01

    The immune system and the role of immunity-related genes have rarely been studied in copepods, even though copepods have a primitive immune response system and also have a potential in pathogen transport higher trophic levels. In this study, we firstly cloned and characterized three core immune genes such as nuclear factor κB (NF-κB), inhibitor of NF-κB (IκB), and lipopolysaccharide-induced TNF-α factor (LITAF) genes in the intertidal copepod Tigriopus japonicus. Several in silico analyses based on conserved domains, motifs, and phylogenetic relationships were supporting their annotations. To investigate the immune-related role of three genes, we exposed lipopolysaccharide (LPS) and two Vibrio sp. to T. japonicus. After exposure of different concentrations of LPS and two Vibrio sp., transcripts of TJ-IκB and TJ-LITAF genes were significantly elevated during the time course in a dose-dependent manner, while TJ-NF-κB transcripts were not significantly changed during exposure. These findings demonstrated that the copepod T. japonicus has a conserved immunity against infection. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Human adipose-derived mesenchymal stem cell-conditioned media suppresses inflammatory bone loss in a lipopolysaccharide-induced murine model.

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    Li, Yu; Gao, Xin; Wang, Jinbing

    2018-02-01

    Conditioned media (CM) from mesenchymal stem cells (MSCs) contains various cytokines, growth factors and microRNAs, which may serve important roles in modulating the inflammatory process. However, the effect of MSC-CM on inflammatory bone loss remains unknown. The present study investigated the effects of conditioned media from human adipose-derived mesenchymal stem cells (AMSC-CM) on the prevention of lipopolysaccharide (LPS)-mediated bone loss in mice. To investigate the underlying mechanisms of this effect, the effects of AMSC-CM on serum levels of inflammation-associated cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 and IL-10] in LPS-treated mice, in addition to their mRNA expression in LPS-treated macrophages, was investigated. Micro-computed tomography and histological analysis revealed that AMSC-CM administration effectively inhibited LPS-induced bone destruction in vivo . ELISA analysis indicated that AMSC-CM significantly reduced the serum levels of proinflammatory cytokines (TNF-α, IL-1 and IL-6) in LPS-treated mice. Furthermore, AMSC-CM treatment significantly decreased the mRNA expression levels of TNF-α, IL-1 and IL-6 in macrophages treated with LPS. These findings indicate that AMSC-CM inhibits LPS-induced bone loss by decreasing the production of proinflammatory cytokines, suggesting that the use of AMSC-CM may be a potential therapeutic strategy for the treatment of inflammatory bone loss.

  11. 1,5-Anhydro-D-fructose attenuates lipopolysaccharide-induced cytokine release via suppression of NF-κB p65 phosphorylation

    International Nuclear Information System (INIS)

    Meng Xiaojie; Kawahara, Ko-ichi; Nawa, Yuko; Miura, Naoki; Shrestha, Binita; Tancharoen, Salunya; Sameshima, Hisayo; Hashiguchi, Teruto; Maruyama, Ikuro

    2009-01-01

    Lipopolysaccharide (LPS) stimulates macrophages by activating NF-κB, which contributes to the release of tumor necrosis factor (TNF)-α and interleukin (IL)-6. 1,5-anhydro-D-fructose (1,5-AF), a monosaccharide formed from starch and glycogen, exhibits anti-oxidant activity and enhances insulin secretion. This study examined the effects of 1,5-AF on LPS-induced inflammatory reactions and elucidated its molecular mechanisms. Before LPS challenge, mice were pretreated with 1,5-AF (38.5 mg/kg). We found that 1,5-AF pretreatment attenuated cytokine release into the serum, including TNF-α, IL-6 and macrophage chemoattractant protein (MCP)-1. Furthermore, pretreatment with 1,5-AF (500 μg/ml) attenuated cytokine release, and 1,5-AF directly inhibited the nuclear translocalization of the NF-κB p65 subunit in LPS-stimulated murine macrophage-like RAW264.7 cells. This inhibition was responsible for decreased LPS-induced phosphorylation on Ser536 of the NF-κB p65 subunit, which is a posttranslational modification involved in the non-canonical pathway. Collectively, these findings indicate that the anti-inflammatory activity of 1,5-AF occurs via inactivation of NF-κB.

  12. Lipopolysaccharide-induced dopaminergic cell death in rat midbrain slice cultures: role of inducible nitric oxide synthase and protection by indomethacin.

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    Shibata, Haruki; Katsuki, Hiroshi; Nishiwaki, Mayumi; Kume, Toshiaki; Kaneko, Shuji; Akaike, Akinori

    2003-09-01

    Glial cell activation associated with inflammatory reaction may contribute to pathogenic processes of neurodegenerative disorders, through production of several cytotoxic molecules. We investigated the consequences of glial activation by interferon-gamma (IFN-gamma)/lipopolysaccharide (LPS) in rat midbrain slice cultures. Application of IFN-gamma followed by LPS caused dopaminergic cell death and accompanying increases in nitrite production and lactate dehydrogenase release. Aminoguanidine, an inhibitor of inducible nitric oxide synthase (iNOS), or SB203580, an inhibitor of p38 mitogen-activated protein kinase, prevented dopaminergic cell loss as well as nitrite production. SB203580 also suppressed expression of iNOS and cyclooxygenase-2 (COX-2) induced by IFN-gamma/LPS. A COX inhibitor indomethacin protected dopaminergic neurons from IFN-gamma/LPS-induced injury, whereas selective COX-2 inhibitors such as NS-398 and nimesulide did not. Notably, indomethacin was able to attenuate neurotoxicity of a nitric oxide (NO) donor. Neutralizing antibodies against tumour necrosis factor-alpha and interleukin-1beta did not inhibit dopaminergic cell death caused by IFN-gamma/LPS, although combined application of these antibodies blocked lactate dehydrogenase release and decrease in the number of non-dopaminergic neurons. These results indicate that iNOS-derived NO plays a crucial role in IFN-gamma/LPS-induced dopaminergic cell death, and that indomethacin exerts protective effect by mechanisms probably related to NO neurotoxicity rather than through COX inhibition.

  13. Gomisin N ameliorates lipopolysaccharide-induced depressive-like behaviors by attenuating inflammation in the hypothalamic paraventricular nucleus and central nucleus of the amygdala in mice

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    Ryota Araki

    2016-10-01

    Full Text Available Emotional impairments such as depressive symptoms often develop in patients with sustained and systemic immune activation. The objective of this study is to investigate the effect of gomisin N, a dibenzocyclooctadiene lignan isolated from the dried fruits of Schisandra chinensis (Turcz. Baill., which exhibited inhibitory effects of the bacterial endotoxin lipopolysaccharide (LPS-induced NO production in a screening assay, on inflammation-induced depressive symptoms. We examined the effects of gomisin N on inflammation induced by LPS in murine microglial BV-2 cells and on LPS-induced behavioral changes in mice. Gomisin N inhibited LPS-induced expression of mRNAs for inflammation-related genes (inducible nitric oxide synthase (iNOS, cyclooxygenase (COX-2, interleukin (IL-1β, IL-6 and tumor necrosis factor (TNF-α in BV-2 cells. Administration of gomisin N attenuated LPS-induced expression of mRNAs for inflammation-related genes, increases in the number of c-Fos immunopositive cells in the hypothalamus and amygdala, depressive-like behavior in the forced swim test and exploratory behavior deficits 24 h after LPS administration in mice. These results suggest that gomisin N might ameliorate LPS-induced depressive-like behaviors through inhibition of inflammatory responses and neural activation in the hypothalamus and amygdala.

  14. Wastes

    International Nuclear Information System (INIS)

    Bovard, Pierre

    The origin of the wastes (power stations, reprocessing, fission products) is determined and the control ensuring the innocuity with respect to man, public acceptance, availability, economics and cost are examined [fr

  15. Suppression of the lipopolysaccharide-induced expression of MARCKS-related protein (MRP) affects transmigration in activated RAW264.7 cells.

    Science.gov (United States)

    Chun, Kwang-Rok; Bae, Eun Mi; Kim, Jae-Kwan; Suk, Kyoungho; Lee, Won-Ha

    2009-01-01

    The molecular action mechanism of MRP, one of the protein kinase C (PKC) substrates, has been under intense investigation, but reports on its role in macrophage function remain controversial. The treatment of macrophage cell lines with bacterial lipopolysaccharide (LPS) induced a high level of MRP expression suggesting that MRP plays a role in the function of activated macrophages. In order to investigate the role of MRP in activated RAW264.7 cells, we stably transfected MRP-specific shRNA expression constructs and tested for alterations in macrophage-related functions. The down-regulation of MRP expression resulted in a marked reduction in chemotaxis toward MCP-1 or extracellular matrix proteins. Furthermore, pharmacological inhibitors of PKC significantly inhibited the chemotaxis in RAW264.7 cells. These data reveals the pivotal role of MRP in the transmigration of activated RAW264.7 cells.

  16. Corn Silk Extract and Its Bioactive Peptide Ameliorated Lipopolysaccharide-Induced Inflammation in Mice via the Nuclear Factor-κB Signaling Pathway.

    Science.gov (United States)

    Ho, Tin-Yun; Li, Chia-Cheng; Lo, Hsin-Yi; Chen, Feng-Yuan; Hsiang, Chien-Yun

    2017-02-01

    Bioactive peptides derived from foods have shown beneficial anti-inflammatory potential. Inhibitory κB kinase-β (IKKβ) plays a crucial role in the activation of nuclear factor-κB (NF-κB), a transcription factor involved in inflammation. Here we applied proteomic and bioinformatics approaches to identify anti-inflammatory peptides that target IKKβ from corn silk. Corn silk extract significantly suppressed lipopolysaccharide (LPS)-induced NF-κB activities [(1.7 ± 0.2)-fold vs (3.0 ± 0.6)-fold, p corn silk also suppressed LPS-induced NF-κB activities [(1.1 ± 0.3)-fold vs 3.3 ± 0.5 fold, p corn silk extract and trypsin hydrolysate significantly inhibited LPS-induced interleukin-1β (IL-1β) production by 58.3 ± 4.5 and 55.1 ± 7.4%, respectively. A novel peptide, FK2, docked into the ATP-binding pocket of IKKβ, was further identified from trypsin hydrolysis of corn silk. FK2 inhibited IKKβ activities, IκB phosphorylation, and subsequent NF-κB activation [(2.3 ± 0.4)-fold vs (5.5 ± 0.4)-fold, p corn silk displayed anti-inflammatory abilities. In addition, we first identified an anti-inflammatory peptide FK2 from corn silk. Moreover, the anti-inflammatory effect of FK2 might be through IKKβ-NF-κB signaling pathways.

  17. Lipopolysaccharide induces VCAM-1 expression and neutrophil adhesion to human tracheal smooth muscle cells: Involvement of Src/EGFR/PI3-K/Akt pathway

    International Nuclear Information System (INIS)

    Lin, W.-N.; Luo, S.-F.; Wu, C.-B.; Lin, C.-C.; Yang, C.-M.

    2008-01-01

    In our previous study, LPS has been shown to induce vascular cell adhesion molecule-1(VCAM-1) expression through MAPKs and NF-κB in human tracheal smooth muscle cells (HTSMCs). In addition to these pathways, the non-receptor tyrosine kinases (Src), EGF receptor (EGFR), and phosphatidylinositol 3-kinase (PI3K) have been shown to be implicated in the expression of several inflammatory target proteins. Here, we reported that LPS-induced up-regulation of VCAM-1 enhanced the adhesion of neutrophils onto HTSMC monolayer, which was inhibited by LY294002 and wortmannin. LPS stimulated phosphorylation of protein tyrosine kinases including Src, PYK2, and EGFR, which were further confirmed using specific anti-phospho-Src, PYK2, or EGFR Ab, respectively, revealed by Western blotting. LPS-stimulated Src, PYK2, EGFR, and Akt phosphorylation and VCAM-1 expression were attenuated by the inhibitors of Src (PP1), EGFR (AG1478), PI3-K (LY294002 and wortmannin), and Akt (SH-5), respectively, or transfection with siRNAs of Src or Akt and shRNA of p110. LPS-induced VCAM-1 expression was also blocked by pretreatment with curcumin (a p300 inhibitor) or transfection with p300 siRNA. LPS-stimulated Akt activation translocated into nucleus and associated with p300 and VCAM-1 promoter region was further confirmed by immunofluorescence, immunoprecipitation, and chromatin immunoprecipitation assays. This association of Akt and p300 to VCAM-1 promoter was inhibited by pretreatment with PP1, AG1478, wortmannin, and SH-5. LPS-induced p300 activation enhanced VCAM-1 promoter activity and VCAM-1 mRNA expression. These results suggested that in HTSMCs, Akt phosphorylation mediated through transactivation of Src/PYK2/EGFR promoted the transcriptional p300 activity and eventually led to VCAM-1 expression induced by LPS

  18. Ginger and Zingerone Ameliorate Lipopolysaccharide-Induced Acute Systemic Inflammation in Mice, Assessed by Nuclear Factor-κB Bioluminescent Imaging.

    Science.gov (United States)

    Hsiang, Chien-Yun; Cheng, Hui-Man; Lo, Hsin-Yi; Li, Chia-Cheng; Chou, Pei-Chi; Lee, Yu-Chen; Ho, Tin-Yun

    2015-07-08

    Ginger is a commonly used spice in cooking. In this study, we comprehensively evaluated the anti-inflammatory activities of ginger and its component zingerone in lipopolysaccharide (LPS)-induced acute systemic inflammation in mice via nuclear factor-κB (NF-κB) bioluminescent imaging. Ginger and zingerone significantly suppressed LPS-induced NF-κB activities in cells in a dose-dependent manner, and the maximal inhibition (84.5% ± 3.5% and 96.2% ± 0.6%) was observed at 100 μg/mL ginger and zingerone, respectively. Moreover, dietary ginger and zingerone significantly reduced LPS-induced proinflammatory cytokine production in sera by 62.9% ± 18.2% and 81.3% ± 6.2%, respectively, and NF-κB bioluminescent signals in whole body by 26.9% ± 14.3% and 38.5% ± 6.2%, respectively. In addition, ginger and zingerone suppressed LPS-induced NF-κB-driven luminescent intensities in most organs, and the maximal inhibition by ginger and zingerone was observed in small intestine. Immunohistochemical staining further showed that ginger and zingerone decreased interleukin-1β (IL-1β)-, CD11b-, and p65-positive areas in jejunum. In conclusion, our findings suggested that ginger and zingerone were likely to be broad-spectrum anti-inflammatory agents in most organs that suppressed the activation of NF-κB, the production of IL-1β, and the infiltration of inflammatory cells in mice.

  19. Inhibiting excessive acidification using zero-valent iron in anaerobic digestion of food waste at high organic load rates.

    Science.gov (United States)

    Kong, Xin; Wei, Yonghong; Xu, Shuang; Liu, Jianguo; Li, Huan; Liu, Yili; Yu, Shuyao

    2016-07-01

    Excessive acidification occurs frequently in food waste (FW) anaerobic digestion (AD) due to the high carbon-to-nitrogen ratio of FW. In this study, zero-valent iron (ZVI) was applied to prevent the excessive acidification. All of the control groups, without ZVI addition (pH∼5.3), produced little methane (CH4) and had high volatile fatty acids/bicarbonate alkalinity (VFA/ALK). By contrast, at OLR of 42.32gVS/Lreactor, the pH of effluent from the reactors with 0.4g/gVSFWadded of ZVI increased to 7.8-8.2, VFA/ALK decreased to <0.1, and the final CH4 yield was ∼380mL/gVSFWadded, suggesting inhibition of excessive acidification. After adding powdered or scrap metal ZVI to the acidogenic reactors, the fractional content of butyric acid changed from 30-40% to 0%, while, that of acetic acid increased. These results indicate that adding ZVI to FW digestion at high OLRs could eliminate excessive acidification by promoting butyric acid conversion and enhancing methanogen activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Ocular Penetration and Anti-inflammatory Activity of Ketorolac 0.45% and Bromfenac 0.09% Against Lipopolysaccharide-Induced Inflammation

    Science.gov (United States)

    Galindo, Danielle; Villanueva, Linda; Nguyen, Cathy; Patel, Milan; Borbridge, Lisa; Attar, Mayssa; Schiffman, Rhett M.; Hollander, David A.

    2011-01-01

    Abstract Purpose Anti-inflammatory activity of topical nonsteroidal anti-inflammatory drugs is mediated by suppression of cyclooxygenase (COX) isoenzymes. This study compared ocular penetration and inflammation suppression of topical ketorolac 0.45% and bromfenac 0.09% ophthalmic solutions in a rabbit model. Methods At hour 0, 36 rabbits received ketorolac 0.45%, bromfenac 0.09%, or an artificial tear 3 times once every 20 min. Half of the rabbits in each group then received intravenous injections of lipopolysaccharide (LPS) and fluorescein isothiocyanate (FITC)–dextran at hour 1, and the other half at hour 10. Aqueous and iris-ciliary body (ICB) samples were collected in the former group at hour 2 (peak) and in the latter group at hour 11 (trough) An additional group of 6 animals received only FITC-dextran, and samples were collected 1 h later. Peak and trough nonsteroidal anti-inflammatory drug concentrations were compared with previously determined half-maximal inhibitory concentrations (IC50) for COX isoenzymes. Results Peak and trough aqueous and ICB concentrations of ketorolac were at least 7-fold or greater than those of bromfenac. At peak levels, both ketorolac 0.45% and bromfenac 0.09% significantly inhibited LPS-induced aqueous prostaglandin E2 and FITC-dextran elevation (P < 0.01). At trough, both study drugs significantly inhibited LPS-induced aqueous prostaglandin E2 elevation (P < 0.05), but only ketorolac 0.45% significantly reduced LPS-induced aqueous FITC-dextran elevation (P < 0.01). Aqueous and ICB ketorolac concentrations exceeded its IC50 for COX-1 and COX-2 at peak and trough. Aqueous and ICB bromfenac levels exceeded its IC50 for COX-2 at peak and trough, but not for COX-1 at trough aqueous levels and peak and trough ICB levels. Conclusions Both ketorolac 0.45% and bromfenac 0.09% effectively suppressed inflammation at peak. At trough, only ketorolac 0.45% effectively suppressed inflammation as measured by FITC

  1. Carbon monoxide-releasing molecule-3 suppresses Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-1β in murine macrophages.

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    Choi, Eun-Young; Choe, So-Hui; Hyeon, Jin-Yi; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2015-10-05

    This study was performed to analyze the effect of carbon monoxide (CO)-releasing molecule-3 (CORM-3) in alleviating the production of proinflammatory mediators in macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen associated with periodontal disease, and its possible mechanisms of action. LPS was isolated using the hot phenol-water method. Culture supernatants were assayed for nitric oxide (NO) and interleukin-1β (IL-1β). Gene expression was quantified by real-time PCR, and protein expression by immunoblotting. DNA-binding activities of NF-κB subunits were determined using an ELISA-based kit. CORM-3 suppressed the production of inducible NO synthase (iNOS)-derived NO and IL-1β at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. CORM-3 enhanced heme oxygenase-1 (HO-1) expression in cells stimulated with P. intermedia LPS, and inhibition of HO-1 activity by SnPP notably reversed the suppressive effect of CORM-3 on LPS-induced production of NO. LPS-induced phosphorylation of p38 and JNK was not affected by CORM-3. CORM-3 did not influence P. intermedia LPS-induced degradation of IκB-α. Instead, nuclear translocation of NF-κB p65 and p50 subunits was blocked by CORM-3 in LPS-treated cells. In addition, CORM-3 reduced LPS-induced p65 and p50 binding to DNA. Besides, CORM-3 significantly suppressed P. intermedia LPS-induced phosphorylation of STAT1. Overall, this study indicates that CORM-3 suppresses the production of NO and IL-1β in P. intermedia LPS-activated murine macrophages via HO-1 induction and inhibition of NF-κB and STAT1 pathways. The modulation of host inflammatory response by CORM-3 would be an attractive therapeutic approach to attenuate the progression of periodontal disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways.

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    Peng, Shuang; Hang, Nan; Liu, Wen; Guo, Wenjie; Jiang, Chunhong; Yang, Xiaoling; Xu, Qiang; Sun, Yang

    2016-05-01

    Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on lipopolysaccharide (LPS)-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum were reduced by andrographolide sulfonate administration. mRNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase (MAPK) as well as p65 subunit of nuclear factor-κB (NF-κB). In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders.

  3. Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways

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    Shuang Peng

    2016-05-01

    Full Text Available Acute lung injury (ALI or acute respiratory distress syndrome (ARDS is a severe, life-threatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection, on lipopolysaccharide (LPS-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF and serum were reduced by andrographolide sulfonate administration. mRNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase (MAPK as well as p65 subunit of nuclear factor-κB (NF-κB. In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders.

  4. Plumbagin, a vitamin K3 analogue, abrogates lipopolysaccharide-induced oxidative stress, inflammation and endotoxic shock via NF-κB suppression.

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    Checker, Rahul; Patwardhan, Raghavendra S; Sharma, Deepak; Menon, Jisha; Thoh, Maikho; Sandur, Santosh K; Sainis, Krishna B; Poduval, T B

    2014-04-01

    Plumbagin has been reported to modulate cellular redox status and suppress NF-κB. In the present study, we investigated the effect of plumbagin on lipopolysaccharide (LPS)-induced endotoxic shock, oxidative stress and inflammatory parameters in vitro and in vivo. Plumbagin inhibited LPS-induced nitric oxide, TNF-α, IL-6 and prostaglandin-E2 production in a concentration-dependent manner in RAW 264.7 cells without inducing any cell death. Plumbagin modulated cellular redox status in RAW cells. Plumbagin treatment significantly reduced MAPkinase and NF-κB activation in macrophages. Plumbagin prevented mice from endotoxic shock-associated mortality and decreased serum levels of pro-inflammatory markers. Plumbagin administration ameliorated LPS-induced oxidative stress in peritoneal macrophages and splenocytes. Plumbagin also attenuated endotoxic shock-associated changes in liver and lung histopathology and decreased the activation of ERK and NF-κB in liver. These findings demonstrate the efficacy of plumbagin in preventing LPS-induced endotoxemia and also provide mechanistic insights into the anti-inflammatory effects of plumbagin.

  5. Portulaca oleracea L. prevents lipopolysaccharide-induced passive avoidance learning and memory and TNF-α impairments in hippocampus of rat.

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    Noorbakhshnia, Maryam; Karimi-Zandi, Leila

    2017-02-01

    There is a growing body of evidence that neuroinflammation can impair memory. It has been indicated that Portulaca oleracea Linn. (POL), possess anti-inflammatory activity and might improve memory disruption caused by inflammation. In this study the effect of pre-treatment with the hydro-alcoholic extract of POL on memory retrieval investigated in lipopolysaccharide (LPS) treated rats. Male Wistar rats (200-220g) received either a control diet or a diet containing of POL (400mg/kg, p.o.) for 14days. Then, they received injections of either saline or LPS (1mg/kg, i.p.). In all the experimental groups, 4h following the last injection, passive avoidance learning (PAL) and memory test was performed. The retention test was done 24h after the training and then the animals were sacrificed. Hippocampal TNF-α levels measured using ELISA as one criteria of LPS-induced neuroinflammation. The results indicated that LPS significantly impaired PAL and memory and increased TNF-α levels in hippocampus tissue. Pre-treatment with POL improved memory in control rats and prevented memory and TNF-α deterioration in LPS treated rats. Taken together, the results of this study suggest that the hydro-alcoholic extract of POL may improve memory deficits in LPS treated rats, possibly via inhibition of TNF-α and anti-inflammatory activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Effect of Three-spot Seahorse Petroleum Ether Extract on Lipopolysaccharide Induced Macrophage RAW264.7 Inflammatory Cytokine Nitric Oxide and Composition Analysis.

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    Chen, LiPing; Shen, XuanRi; Chen, GuoHua; Cao, XianYing; Yang, Jian

    2015-01-01

    Three-Spot seahorse is a traditional medicine in Asian countries. However, the alcohol extract is largely unknown for its anti-inflammatory activity. This study aimed at elucidating fraction of potent anti-inflammatory activity of seahorse. A systematic solvent extraction method of liquid-liquid fractionation of ethanol crude extract gave four fractions petroleum ether (PE), and ethyl acetate (EtOAc), water saturated butanol (n-BuOH), water (H2O). In this study, PE extract was selected for further study after preliminary screening test, and was connected to silica column chromatography and eluted with different polarity of mobile phases, and obtained four active fractions (Fr I, Fr II, Fr III, Fr IV). Effect of separated fractions on inflammation was investigated in lipopolysaccharide (LPS) stimulated murine RAW264.7 cells in vitro. The result shows that seahorse extract was capable of inhibiting the production of nitric oxide (NO) significantly in a dose dependent manner and exhibited no notable cytotoxicity on cell viability. IC50 of fraction IV was 36.31 μg/mL, indicating that separated fraction possessed potent NO inhibitory activity against LPS-induced inflammatory response, thus, demonstrated its in vitro anti-inflammatory potentiality, it may be at least partially explained by the presence of anti-inflammation active substances, phenolic compounds, phospholipids and polyunsaturated fatty acids, especially phospholipids and polyunsaturated fatty acids. It could be suggested that seahorse lipid-soluble components could be used in functional food and anti-inflammatory drug preparations.

  7. Opposite effects of methanandamide on lipopolysaccharide-induced prostaglandin E2 and F2α synthesis in uterine explants from pregnant mice.

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    Claudia A Vercelli

    Full Text Available Prostaglandins (PG are effective abortifacients and are important mediators of lipopolisaccharide (LPS-induced embryonic resorption (ER. Besides, anandamide (AEA has been described as one of the major endocannabinoids present in the uterus suggesting that it might play a role in reproduction. It has been reported that high levels of AEA are associated with pregnancy failure and that LPS increases AEA production. Also, it has been observed that AEA modulates PG production in different tissues. In this sense, we studied whether LPS-induced PG production is modulated by AEA and we also assessed the effect of this endocannabinoid on PG metabolism in an in vitro model. Uterine explants from BALB/c implantation sites were cultured in the presence of LPS plus cannabinoid receptor (CB specific antagonists and PG production was assessed. Then, we studied the effect of exogenous AEA on different steps of PG metabolic pathway. We showed that AEA is involved in LPS-induced PG biosynthesis. Also, we observed that AEA exerts opposite effects on PGE(2 and PGF(2α biosynthesis, by inhibiting PGE(2 production and increasing PGF(2α levels. We suggest that AEA could be involved in the mechanisms implicated in LPS-induced ER. A better understanding of how AEA could be affecting ER could help developing specific interventions to prevent this pathology.

  8. Bigelovii A Protects against Lipopolysaccharide-Induced Acute Lung Injury by Blocking NF-κB and CCAAT/Enhancer-Binding Protein δ Pathways

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    Chunguang Yan

    2016-01-01

    Full Text Available Optimal methods are applied to acute lung injury (ALI and the acute respiratory distress syndrome (ARDS, but the mortality rate is still high. Accordingly, further studies dedicated to identify novel therapeutic approaches to ALI are urgently needed. Bigelovii A is a new natural product and may exhibit anti-inflammatory activity. Therefore, we sought to investigate its effect on lipopolysaccharide- (LPS- induced ALI and the underlying mechanisms. We found that LPS-induced ALI was significantly alleviated by Bigelovii A treatment, characterized by reduction of proinflammatory mediator production, neutrophil infiltration, and lung permeability. Furthermore, Bigelovii A also downregulated LPS-stimulated inflammatory mediator expressions in vitro. Moreover, both NF-κB and CCAAT/enhancer-binding protein δ (C/EBPδ activation were obviously attenuated by Bigelovii A treatment. Additionally, phosphorylation of both p38 MAPK and ERK1/2 (upstream signals of C/EBPδ activation in response to LPS challenge was also inhibited by Bigelovii A. Therefore, Bigelovii A could attenuate LPS-induced inflammation by suppression of NF-κB, inflammatory mediators, and p38 MAPK/ERK1/2—C/EBPδ, inflammatory mediators signaling pathways, which provide a novel theoretical basis for the possible application of Bigelovii A in clinic.

  9. Amomum tsao-ko suppresses lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages via Nrf2-dependent heme oxygenase-1 expression.

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    Li, Bin; Choi, Hee-Jin; Lee, Dong-Sung; Oh, Hyuncheol; Kim, Youn-Chul; Moon, Jin-Young; Park, Won-Hwan; Park, Sun-Dong; Kim, Jai-Eun

    2014-01-01

    Amomum tsao-ko Crevost et Lemaire, used as a spice in Asia, is an important source of Chinese cuisine and traditional Chinese medicines. A. tsao-ko is reported to exert a variety of biological and pharmacological activities, including anti-proliferative, anti-oxidative and neuroprotective effects. In this study, NNMBS227, consisting of the ethanol extract of A. tsao-ko, exhibited potent anti-inflammatory activities in RAW264.7 macrophages. We investigated the effect of NNMBS227 in the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-α and interleukin-1β) in LPS stimulated macrophages. NNMBS227 also inhibited the phosphorylation and degradation of IκB-α, as well as the nuclear translocation of nuclear factor kappa B (NF-κB) p65 caused by stimulation with LPS. In addition, NNMBS227 induced heme oxygenase (HO)-1 expression through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in macrophages. Using tin protoporphyrin (SnPP), an HO activity inhibitor, we confirmed an association between the anti-inflammatory effects of NNMBS227 and the up-regulation of HO-1. These findings suggest that Nrf2-dependent increases in the expression of HO-1 induced by NNMBS227 conferred anti-inflammatory activities in LPS stimulated RAW264.7 macrophages.

  10. Protective effects of telmisartan and tempol on lipopolysaccharide-induced cognitive impairment, neuroinflammation, and amyloidogenesis: possible role of brain-derived neurotrophic factor.

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    Khallaf, Waleed A I; Messiha, Basim A S; Abo-Youssef, Amira M H; El-Sayed, Nesrine S

    2017-07-01

    Angiotensin II has pro-inflammatory and pro-oxidant potentials. We investigated the possible protective effects of the Angiotensin II receptor blocker telmisartan, compared with the superoxide scavenger tempol, on lipopolysaccharide (LPS)-induced cognitive decline and amyloidogenesis. Briefly, mice were allocated into a normal control group, an LPS control group, a tempol treatment group, and 2 telmisartan treatment groups. A behavioral study was conducted followed by a biochemical study via assessment of brain levels of beta amyloid (Aβ) and brain-derived neurotropic factor (BDNF) as amyloidogenesis and neuroplasticity markers, tumor necrosis factor alpha (TNF-α), nitric oxide end products (NOx), neuronal and inducible nitric oxide synthase (nNOS and iNOS) as inflammatory markers, and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione reduced (GSH), and nitrotyrosine (NT) as oxido-nitrosative stress markers. Finally, histopathological examination of cerebral cortex, hippocampus, and cerebellum sections was performed using routine and special Congo red stains. Tempol and telmisartan improved cognition, decreased brain Aβ deposition and BDNF depletion, decreased TNF-α, NOx, nNOS, iNOS, MDA, and NT brain levels, and increased brain SOD and GSH contents, parallel to confirmatory histopathological evidences. In conclusion, tempol and telmisartan are promising drugs in managing cognitive impairment and amyloidogenesis, at least via upregulation of BDNF with inhibition of neuroinflammation and oxido-nitrosative stress.

  11. Activation of the cholinergic anti-inflammatory pathway by nicotine ameliorates lipopolysaccharide-induced preeclampsia-like symptoms in pregnant rats.

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    Liu, Yuanyuan; Yang, Jinying; Bao, Junjie; Li, Xiaolan; Ye, Aihua; Zhang, Guozheng; Liu, Huishu

    2017-01-01

    Preeclampsia (PE) exerts a more intense systemic inflammatory response than normal pregnancy. Recently, the role of the cholinergic anti-inflammatory pathway (CAP) in regulating inflammation has been extensively studied. The aim of this study was to investigate the effect of nicotine, a selective cholinergic agonist, on lipopolysaccharide (LPS)-induced preeclampsia-like symptoms in pregnant rats and to determine the molecular mechanism underlying it. Rats were administered LPS (1.0 μg/kg) via tail vein injection on gestational day 14 to induce preeclampsia-like symptoms. Nicotine (1.0 mg/kg/d) and α-bungarotoxin (1.0 μg/kg/d) were injected subcutaneously into the rats from gestational day 14-19. Clinical symptoms were recorded. Serum and placentas were collected to determine cytokine levels using Luminex. The mRNA and protein expression levels of α7 nicotinic acetylcholine receptor (α7nAChR) were determined using Real time-PCR and Western blot analysis. Immunohistochemistry was performed to determine the level of activation of nuclear factor-κB (NF-κB) in placentas. Nicotine significantly ameliorated LPS-induced preeclampsia-like symptoms in pregnant rats (P preeclampsia (P preeclampsia rats. Our findings suggest that the activation of α7nAChR by nicotine attenuates preeclampsia-like symptoms, and this protective effect is likely the result of the inhibition of inflammation via the NF-κB p65 pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. DNA methylcytosine dioxygenase ten-eleven translocation 2 enhances lipopolysaccharide-induced cytokine expression in human dental pulp cells by regulating MyD88 hydroxymethylation.

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    Wang, Xinxuan; Feng, Zhihui; Li, Qimeng; Yi, Baicheng; Xu, Qiong

    2018-04-13

    Dental pulp inflammation is a bacterially driven inflammation process characterized by the local accumulation of cytokines/chemokines that participate in destructive processes in the pulp. Multiple mechanisms are involved in dental pulp inflammation, including epigenetic events, such as DNA methylation/demethylation. Ten-eleven translocation 2 (TET2) is a recently discovered DNA methylcytosine dioxygenase that plays important roles in inflammatory disease. However, its role in the inflammatory response of dental pulp is unknown. We observed elevated mRNA and protein levels of TET2 after lipopolysaccharide (LPS) stimulation in human dental pulp cells (hDPCs). To identify the effects of TET2 on cytokine expression, TET2 was knocked down and cytokines were detected using a cytokine antibody array after LPS stimulation. The protein expression of GM-CSF, IL-6, IL-8 and RANTES decreased in the LPS-induced hDPCs following TET2 knockdown. The downregulated expression levels of IL-6 and IL-8 were further confirmed by real-time quantitative polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Additionally, the phosphorylation levels of IKK-α/β, p65 and IκBα of the NF-κB signaling pathway were decreased in the TET2-silenced group. Furthermore, the global 5-hydroxymethylcytosine (5hmC) level was significantly decreased and the genomic 5-methylcytosine (5mC) level was increased in the TET2-deficient hDPCs; TET2 depletion resulted in a decrease in the 5hmC level of the MyD88 promoter following LPS stimulation. These findings indicate that TET2 knockdown inhibits LPS-induced inflammatory response in hDPCs by downregulating MyD88 hydroxymethylation. Thus, TET2-dependent DNA demethylation might play an important role in dental pulp inflammation as an epigenetic regulator.

  13. Role of human amnion-derived mesenchymal stem cells in promoting osteogenic differentiation by influencing p38 MAPK signaling in lipopolysaccharide -induced human bone marrow mesenchymal stem cells

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    Wang, Yuli; Wu, Hongxia; Shen, Ming; Ding, Siyang; Miao, Jing; Chen, Ning

    2017-01-01

    Periodontitis is a chronic inflammatory disease induced by bacterial pathogens, which not only affect connective tissue attachments but also cause alveolar bone loss. In this study, we investigated the anti-inflammatory effects of Human amnion-derived mesenchymal stem cells (HAMSCs) on human bone marrow mesenchymal stem cells (HBMSCs) under lipopolysaccharide (LPS)-induced inflammatory conditions. Proliferation levels were measured by flow cytometry and immunofluorescence staining of 5-ethynyl-2′-deoxyuridine (EdU). Osteoblastic differentiation and mineralization were investigated using chromogenic alkaline phosphatase activity (ALP) activity substrate assays, Alizarin red S staining, and RT-PCR analysis of HBMSCs osteogenic marker expression. Oxidative stress induced by LPS was investigated by assaying reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity. Here, we demonstrated that HAMSCs increased the proliferation, osteoblastic differentiation, and SOD activity of LPS-induced HBMSCs, and down-regulated the ROS level. Moreover, our results suggested that the activation of p38 MAPK signal transduction pathway is essential for reversing the LPS-induced bone-destructive processes. SB203580, a selective inhibitor of p38 MAPK signaling, significantly suppressed the anti-inflammatory effects in HAMSCs. In conclusion, HAMSCs show a strong potential in treating inflammation-induced bone loss by influencing p38 MAPK signaling. - Highlights: • LPS inhibites osteogenic differentiation in HBMSCs via suppression of p38 MAPK signaling pathway. • HAMSCs promote LPS-induced HBMSCs osteogenic differentiation through p38 MAPK signaling pathway. • HAMSCs reverse LPS-induced oxidative stress in LPS-induced HBMSCs through p38 MAPK signaling pathway.

  14. Proteomic analysis of the effects of aged garlic extract and its FruArg component on lipopolysaccharide-induced neuroinflammatory response in microglial cells.

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    Hui Zhou

    Full Text Available Aged garlic extract (AGE is widely used as a dietary supplement, and is claimed to promote human health through anti-oxidant/anti-inflammatory activities with hypolipidemic, antiplatelet and neuroprotective effects. Prior studies of AGE have mainly focused on its organosulfur compounds, with little attention paid to its carbohydrate derivatives, such as N-α-(1-deoxy-D-fructos-1-yl-L-arginine (FruArg. The goal of this study is to investigate actions of AGE and FruArg on antioxidative and neuroinflammatory responses in lipopolysaccharide (LPS-activated murine BV-2 microglial cells using a proteomic approach. Our data show that both AGE and FruArg can significantly inhibit LPS-induced nitric oxide (NO production in BV-2 cells. Quantitative proteomic analysis by combining two dimensional differential in-gel electrophoresis (2D-DIGE with mass spectrometry revealed that expressions of 26 proteins were significantly altered upon LPS exposure, while levels of 20 and 21 proteins exhibited significant changes in response to AGE and FruArg treatments, respectively, in LPS-stimulated BV-2 cells. Notably, approximate 78% of the proteins responding to AGE and FruArg treatments are in common, suggesting that FruArg is a major active component of AGE. MULTICOM-PDCN and Ingenuity Pathway Analyses indicate that the proteins differentially affected by treatment with AGE and FruArg are involved in inflammatory responses and the Nrf2-mediated oxidative stress response. Collectively, these results suggest that AGE and FruArg attenuate neuroinflammatory responses and promote resilience in LPS-activated BV-2 cells by suppressing NO production and by regulating expression of multiple protein targets associated with oxidative stress.

  15. Interaction in endothelium of non-muscular myosin light-chain kinase and the NF-κB pathway is critical to lipopolysaccharide-induced vascular hyporeactivity.

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    Recoquillon, Sylvain; Carusio, Nunzia; Lagrue-Lakhal, Anne-Hélène; Tual-Chalot, Simon; Filippelli, Amelia; Andriantsitohaina, Ramaroson; Martinez, M Carmen

    2015-10-01

    During sepsis, endothelial barrier dysfunction contributes to cardiovascular failure, mainly through the release of oxidative metabolites by penetrant leukocytes. We reported the non-muscular isoform of myosin light chain kinase (nmMLCK) playing a pivotal role in endotoxin shock injury associated with oxidative and nitrative stresses, and vascular hyporeactivity. The present study was aimed at understanding the molecular mechanism of lipopolysaccharide (LPS)-induced vascular alterations as well as studying a probable functional association of nmMLCK with nuclear factor κ-light-chain enhancer of activated B cells (NF-κB). Aortic rings from mice were exposed in vitro to LPS and, then, vascular reactivity was measured. Human aortic endothelial cells (HAoECs) were incubated with LPS, and interaction of nmMLCK with NF-κB was analysed. We provide evidence that nmMLCK deletion prevents vascular hyporeactivity induced by in vitro LPS treatment but not endothelial dysfunction in the aorta. Deletion of nmMLCK inhibits LPS-induced NF-κB activation and increases nitric oxide (NO) release via induction of inducible NO synthase (iNOS) within the vascular wall. Also, removal of endothelium prevented both NF-κB and iNOS expression in aortic rings. Among the proinflammatory factors released by LPS-treated endothelial cells, interleukin-6 accounts for the induction of iNOS on smooth muscle cells in response to LPS. Of particular interest is the demonstration that, in HAoECs, LPS-induced NF-κB activation occurs via increased MLCK activity sensitive to the MLCK inhibitor, ML-7, and physical interactions between nmMLCK and NF-κB. We report for the first time on NF-κB as a novel partner of nmMLCK within endothelial cells. The present study demonstrates a pivotal role of nmMLCK in vascular inflammatory pathologies. © 2015 Authors; published by Portland Press Limited.

  16. Genistein suppresses Prevotella intermedia lipopolysaccharide-induced inflammatory response in macrophages and attenuates alveolar bone loss in ligature-induced periodontitis.

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    Choi, Eun-Young; Bae, Seung Han; Ha, Min Hee; Choe, So-Hui; Hyeon, Jin-Yi; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2016-02-01

    Genistein is a major isoflavone subclass of flavonoids found in soybean and a potent tyrosine kinase inhibitor. The present study aimed to assess the effect of genistein on the production of proinflammatory mediators in murine macrophages stimulated with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogen associated with different forms of periodontal disease, and to evaluate its possible influence on alveolar bone loss in ligature-induced periodontitis using micro-computed tomography (micro-CT) analysis as well. LPS was isolated from P. intermedia ATCC 25611 by using the standard hot phenol-water method. Culture supernatants were analyzed for nitric oxide (NO) and interleukin-6 (IL-6). Inducible NO synthase (iNOS) protein expression was evaluated by immunoblot analysis. Real-time PCR was carried out to measure iNOS and IL-6 mRNA expression. In addition, effect of genistein on alveolar bone loss was evaluated in a rat model of experimental periodontitis using micro-CT analysis. Genistein significantly attenuated P. intermedia LPS-induced production of iNOS-derived NO and IL-6 with attendant decrease in their mRNA expression in RAW264.7 cells. In addition, when genistein was administered to rats, decreases in alveolar bone height and bone volume fraction induced by ligature placement were significantly inhibited. Genistein administration also prevented ligature-induced alterations in the microstructural parameters of trabecular bone, including trabecular thickness, trabecular separation, bone mineral density and structure model index. While additional studies are required, we suggest that genistein could be utilized for the therapy of human periodontitis in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Folic acid protects against lipopolysaccharide-induced preterm delivery and intrauterine growth restriction through its anti-inflammatory effect in mice.

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    Mei Zhao

    Full Text Available Increasing evidence demonstrates that maternal folic acid (FA supplementation during pregnancy reduces the risk of neural tube defects, but whether FA prevents preterm delivery and intrauterine growth restriction (IUGR remains obscure. Previous studies showed that maternal lipopolysaccharide (LPS exposure induces preterm delivery, fetal death and IUGR in rodent animals. The aim of this study was to investigate the effects of FA on LPS-induced preterm delivery, fetal death and IUGR in mice. Some pregnant mice were orally administered with FA (0.6, 3 or 15 mg/kg 1 h before LPS injection. As expected, a high dose of LPS (300 μg/kg, i.p. on gestational day 15 (GD15 caused 100% of dams to deliver before GD18 and 89.3% of fetuses dead. A low dose of LPS (75 μg/kg, i.p. daily from GD15 to GD17 resulted in IUGR. Interestingly, pretreatment with FA prevented LPS-induced preterm delivery and fetal death. In addition, FA significantly attenuated LPS-induced IUGR. Further experiments showed that FA inhibited LPS-induced activation of nuclear factor kappa B (NF-κB in mouse placentas. Moreover, FA suppressed LPS-induced NF-κB activation in human trophoblast cell line JEG-3. Correspondingly, FA significantly attenuated LPS-induced upregulation of cyclooxygenase (COX-2 in mouse placentas. In addition, FA significantly reduced the levels of interleukin (IL-6 and keratinocyte-derived cytokine (KC in amniotic fluid of LPS-treated mice. Collectively, maternal FA supplementation during pregnancy protects against LPS-induced preterm delivery, fetal death and IUGR through its anti-inflammatory effects.

  18. Ganoderma lucidum Polysaccharides Reduce Lipopolysaccharide-Induced Interleukin-1β Expression in Cultured Smooth Muscle Cells and in Thoracic Aortas in Mice

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    Chan-Jung Liang

    2014-01-01

    Full Text Available The expression of inflammatory cytokines on vascular walls is a critical event in vascular diseases and inflammation. The aim of the present study was to examine the effects of an extract of Ganoderma lucidum (Reishi polysaccharides (EORPs, which is effective against immunological disorders, on interleukin- (IL- 1β expression by human aortic smooth muscle cells (HASMCs and the underlying mechanism. The lipopolysaccharide- (LPS- induced IL-1β expression was significantly reduced when HASMCs were pretreated with EORP by Western blot and immunofluorescent staining. Pretreatment with 10 μg/mL EORP decreased LPS-induced ERK, p38, JNK, and Akt phosphorylation. But the increase in IL-1β expression with LPS treatment was only inhibited by pretreatment with the ERK1/2 inhibitor, while the JNK and p38 inhibitors had no effect. In addition, EORP reduced the phosphorylation and nuclear translocation of nuclear factor- (NF- κB p65 in LPS-treated HASMCs. Furthermore, in vivo, IL-1β expression was strongly expressed in thoracic aortas in LPS-treated mice. Oral administration of EORP decreased IL-1β expression. The level of IL-1β expression in LPS-treated or in LPS/EORP-treated group was very low and was similar to that of the saline-treated group in toll-like receptor 4-deficient (TLR4−/− mice. These findings suggest that EORP has the anti-inflammatory property and could prove useful in the prevention of vascular diseases and inflammatory responses.

  19. Histone deacetylase inhibitors restore IL-10 expression in lipopolysaccharide-induced cell inflammation and reduce IL-1β and IL-6 production in breast silicone implant in C57BL/6J wild-type murine model.

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    Di Liddo, Rosa; Valente, Sergio; Taurone, Samanta; Zwergel, Clemens; Marrocco, Biagina; Turchetta, Rosaria; Conconi, Maria Teresa; Scarpa, Carlotta; Bertalot, Thomas; Schrenk, Sandra; Mai, Antonello; Artico, Marco

    2016-01-20

    Among epigenetic enzymes, histone deacetylases (HDACs) are responsible for regulating the expression of an extensive array of genes by reversible deacetylation of nuclear histones as well as a large number of non-histone proteins. Initially proposed for cancer therapy, recently the interest for HDAC inhibitors (HDACi) as orally active, safe, and anti-inflammatory agents is rising due to their ability in reducing the severity of inflammatory and autoimmune diseases. In particular, selective HDAC3, HDAC6, and HDAC8 inhibitors have been described to downregulate the expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-1β, and IL-6). Herein, using KB31, C2C12, and 3T3-J2 cell lines, we demonstrated that, under lipopolysaccharide-induced in vitro inflammation, HDAC3/6/8 inhibitor MC2625 and HDAC6-selective inhibitor MC2780 were effective at a concentration of 30 ng/mL to downregulate mRNA expression of pro-inflammatory cytokines (IL-1β and IL-6) and to promote the transcription of IL-10 gene, without affecting the cell viability. Afterwards, we investigated by immunohistochemistry the activity of MC2625 and MC2780 at a concentration of 60 ng/kg animal weight to regulate silicone-triggered immune response in C57BL/6J female mice. Our findings evidenced the ability of such inhibitors to reduce host inflammation in silicone implants promoting a thickness reduction of peri-implant fibrous capsule, upregulating IL-10 expression, and reducing the production of both IL-1β and IL-6. These results underline the potential application of MC2625 and MC2780 in inflammation-related diseases.

  20. κ-Carrageenan Enhances Lipopolysaccharide-Induced Interleukin-8 Secretion by Stimulating the Bcl10-NF-κB Pathway in HT-29 Cells and Aggravates C. freundii-Induced Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Wei Wu

    2017-01-01

    Full Text Available Background. The dietary usage of carrageenan as common food additive has increased observably over the last 50 years. But there is substantial controversy about its safety. Methods. We investigated whether the κ-carrageenan could enhance lipopolysaccharide-induced IL-8 expression by studying its actions on the TLR4-NF-κB pathway. The aggravating effect of κ-carrageenan on Citrobacter freundii DBS100-induced intestinal inflammation was also investigated in a mouse model. Results. Our data show that κ-carrageenan pretreatment promoted LPS-induced IL-8 expression in HT-29 cells. Although CD14, MD-2, and TLR4 were upregulated, the binding of LPS was not enhanced. However, the pathway of Bcl10-NF-κB was triggered. Interestingly, κ-carrageenan competitively blocked the binding of FITC-LPS. Furthermore, pretreatment with κ-carrageenan for one week previous to gavage with C. freundii DBS100 markedly aggravated weight loss, mortality, and colonic damage. The secretion of cytokines was unbalanced and the ratio of Tregs was decreased significantly. In addition, κ-carrageenan, together with C. freundii DBS100, enhanced the transcription and secretion of TLR4 and NF-κB. Conclusions. κ-Carrageenan can synergistically activate LPS-induced inflammatory through the Bcl10-NF-κB pathway, as indicated by its aggravation of C. freundii DBS100-induced colitis in mice. General Significance. Our results suggest that κ-carrageenan serves as a potential inflammatory agent that magnifies existing intestinal inflammation.

  1. Suaeda japonica Makino Attenuates Lipopolysaccharide- Induced ...

    African Journals Online (AJOL)

    HP

    Tropical Journal of Pharmaceutical Research June 2013; 12 (3): 351-356 ... expression and production of inflammatory mediators determined by Western blot analysis. Results: SJE significantly ..... This work was supported by Business for.

  2. Hara on lipopolysaccharide-induced neuroinflammation

    African Journals Online (AJOL)

    read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,.

  3. The root barks of Morus alba and the flavonoid constituents inhibit airway inflammation.

    Science.gov (United States)

    Lim, Hun Jai; Jin, Hong-Guang; Woo, Eun-Rhan; Lee, Sang Kook; Kim, Hyun Pyo

    2013-08-26

    The root barks of Morus alba have been used in traditional medicine as an anti-inflammatory drug, especially for treating lung inflammatory disorders. To find new alternative agents against airway inflammation and to establish the scientific rationale of the herbal medicine in clinical use, the root barks of Morus alba and its flavonoid constituents were examined for the first time for their pharmacological activity against lung inflammation. For in vivo evaluation, an animal model of lipopolysaccharide-induced airway inflammation in mice was used. An inhibitory action against the production of proinflammatory molecules in lung epithelial cells and lung macrophages was examined. Against lipopolysaccharide-induced airway inflammation, the ethanol extract of the root barks of Morus alba clearly inhibited bronchitis-like symptoms, as determined by TNF-α production, inflammatory cells infiltration and histological observation at 200-400mg/kg/day by oral administration. In addition, Morus alba and their major flavonoid constituents including kuwanone E, kuwanone G and norartocarpanone significantly inhibited IL-6 production in lung epithelial cells (A549) and NO production in lung macrophages (MH-S). Taken together, it is concluded that Morus alba and the major prenylated flavonoid constituents have a potential for new agents to control lung inflammation including bronchitis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. The effect of sulfur on the inhibition of PCDD/F formation during co-combustion of coal and solid waste

    Energy Technology Data Exchange (ETDEWEB)

    Palladas, A. [Laboratory of Environmental and Energy Processes, Thermi-Thessaloniki (Greece). Chemical Process Engineering Research Institute; Samaras, P. [TEI of Western Macedonia, Kozani (Greece). Dept. of Environmental Technology; Sakellaropoulos, G. [Aristotle Univ. of Thessaloniki (Greece). Dept. of Chemical Engineering

    2004-09-15

    Co-combustion of solid wastes with coal is a promising technique used to reduce landfilled wastes, utilizing waste the energy content. However, solid wastes often contain chlorine and other substances, which upon combustion may result in the production of extremely toxic compounds like polychlorinated dibenzo-p-dioxins and dibenzofurans. Various compounds have been proposed for their inhibition ability of PCDD/F formation, including sulphuric and nitrogen containing substances. Sulfur compounds may form some kind of complexes with metal species, reducing thus their ability for catalysing the PCDD/F formation pathways. Sulfur inhibitory capacity has been attributed to reaction with copper catalytic sites, altering their form and presumably their ability to produce Cl{sub 2} through the Deacon process reaction. Another second postulated role of sulfur is to undergo homogeneous reactions, converting the primary chlorinating agent, Cl{sub 2}, into a form (HCl) less likely to undergo aromatic substitution reactions forming PCDD/F precursors. The objectives of this work were the measurement of PCDD/F emissions during co-combustion of different fuel mixtures, and the study of the effect of sulfur addition to the fuel on PCDD/F formation.

  5. Inhibition of protease-resistant prion protein formation in a transformed deer cell line infected with chronic wasting disease

    NARCIS (Netherlands)

    Raymond, G.J.; Olsen, E.A.; Lee, K.S.; Raymond, L.D.; Bryant, P.K.; Baron, G.S.; Caughey, W.S.; Kocisko, D.A.; McHolland, L.E.; Favara, C.; Langeveld, J.P.M.; Zijderveld, van F.G.; Mayer, R.T.; Miller, M.W.; Williams, E.S.; Caughey, B.

    2006-01-01

    Chronic wasting disease (CWD) is an emerging transmissible spongiform encephalopathy (prion disease) of North American cervids, i.e., mule deer, white-tailed deer, and elk (wapiti). To facilitate in vitro studies of CWD, we have developed a transformed deer cell line that is persistently infected

  6. Okra (Abelmoschus esculentus Linn) inhibits lipopolysaccharide ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research June 2017; 16 (6): 1285-1292 ... lipopolysaccharide-induced inflammatory mediators in .... Multiple comparison of data was carried out by one-way. ANOVA followed by Bonferroni post-tests. P <.

  7. Antioxidant activities of aqueous extract from Stevia rebaudiana stem waste to inhibit fish oil oxidation and identification of its phenolic compounds.

    Science.gov (United States)

    Yu, Hui; Yang, Gangqiang; Sato, Minoru; Yamaguchi, Toshiyasu; Nakano, Toshiki; Xi, Yinci

    2017-10-01

    We investigated the potential for exploiting Stevia rebaudiana stem (SRS) waste as a source of edible plant-based antioxidants finding for the first time that the hot water extract of SRS had significantly higher antioxidant activity against fish oil oxidation than that of the leaf, despite SRS extract having lower total phenolic content, DPPH radical scavenging activity and ORAC values. To locate the major antioxidant ingredients, SRS extract was fractionated using liquid chromatography. Five phenolic compounds (primary antioxidant components in activity-containing fractions) were identified by NMR and HR-ESI-MS: vanillic acid 4-O-β-d-glucopyranoside (1), protocatechuic acid (2), caffeic acid (3), chlorogenic acid (4) and cryptochlorogenic acid (5). Further analysis showed that, among compounds 2-5, protocatechuic acid had the highest capacity to inhibit peroxides formation, but exhibited the lowest antioxidant activities in DPPH and ORAC assays. These results indicate that SRS waste can be used as strong natural antioxidant materials in the food industry. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Complete reversal of muscle wasting in experimental cancer cachexia: Additive effects of activin type II receptor inhibition and β-2 agonist.

    Science.gov (United States)

    Toledo, Míriam; Busquets, Sílvia; Penna, Fabio; Zhou, Xiaolan; Marmonti, Enrica; Betancourt, Angelica; Massa, David; López-Soriano, Francisco J; Han, H Q; Argilés, Josep M

    2016-04-15

    Formoterol is a highly potent β2-adrenoceptor-selective agonist, which is a muscle growth promoter in many animal species. Myostatin/activin inhibition reverses skeletal muscle loss and prolongs survival of tumor-bearing animals. The aim of this investigation was to evaluate the effects of a combination of the soluble myostatin receptor ActRIIB (sActRIIB) and the β2-agonist formoterol in the cachectic Lewis lung carcinoma model. The combination of formoterol and sActRIIB was extremely effective in reversing muscle wasting associated with experimental cancer cachexia in mice. Muscle weights from tumor-bearing animals were completely recovered following treatment and this was also reflected in the measured grip strength. This combination increased food intake in both control and tumor-bearing animals. The double treatment also prolonged survival significantly without affecting the weight and growth of the primary tumor. In addition, it significantly reduced the number of metastasis. Concerning the mechanisms for the preservation of muscle mass during cachexia, the effects of formoterol and sActRIIB seemed to be additive, since formoterol reduced the rate of protein degradation (as measured in vitro as tyrosine release, using incubated isolated individual muscles) while sActRIIB only affected protein synthesis (as measured in vivo using tritiated phenylalanine). Formoterol also increased the rate of protein synthesis and this seemed to be favored by the presence of sActRIIB. Combining formoterol and sActRIIB seemed to be a very promising treatment for experimental cancer cachexia. Further studies in human patients are necessary and may lead to a highly effective treatment option for muscle wasting associated with cancer. © 2015 UICC.

  9. Lipopolysaccharide-induced pulmonary inflammation is not accompanied by a release of anandamide into the lavage fluid or a down-regulation of the activity of fatty acid amide hydrolase

    DEFF Research Database (Denmark)

    Holt, S.; J. Fowler, C.; Rocksén, D.

    2004-01-01

    The effect of lipopolysaccharide inhalation upon lung anandamide levels, anandamide synthetic enzymes and fatty acid amide hydrolase has been investigated. Lipopolysaccharide exposure produced a dramatic extravasation of neutrophils and release of tumour necrosis factor a into the bronchoalveolar......-acyltransferase and N-acylphosphatidylethanolamine phospholipase D and the activity of fatty acid amide hydrolase in lung membrane fractions did not change significantly following the exposure to lipopolysaccharide. The non-selective fatty acid amide hydrolase inhibitor phenylmethylsulfonyl fluoride was a less potent...... inhibitor of lung fatty acid amide hydrolase than expected from the literature, and a dose of 30 mg/kg i.p. of this compound, which produced a complete inhibition of brain anandamide metabolism, only partially inhibited the lung metabolic activity....

  10. Glycyrrhetinic acid attenuates lipopolysaccharide-induced fulminant hepatic failure in D-galactosamine-sensitized mice by up-regulating expression of interleukin-1 receptor-associated kinase-M

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Xinru [Department of Pharmacology, Chongqing Medical University, Chongqing 400016 (China); Gong, Xia [Department of Anatomy, Chongqing Medical University, Chongqing 400016 (China); Zhang, Li; Jiang, Rong [Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016 (China); Kuang, Ge [Department of Pharmacology, Chongqing Medical University, Chongqing 400016 (China); Wang, Bin [Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chen, Xinyu [Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021 (China); Wan, Jingyuan, E-mail: jywan@cqmu.edu.cn [Department of Pharmacology, Chongqing Medical University, Chongqing 400016 (China)

    2017-04-01

    Glycyrrhetinic acid (GA), the main active ingredient of licorice, reportedly has anti-inflammatory and hepatoprotective properties, but its molecular mechanisms remain be elusive. In the present study, Balb/c mice were pretreated with GA (10, 30, or 100 mg/kg) 1 h before lipopolysaccharide (LPS)/D-galactosamine (D-GalN) administration. In other in vitro experiment, RAW264.7 macrophages were pretreated with GA before LPS exposure. The mortality, hepatic tissue histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Toll like receptor 4 (TLR4), interleukin-1 receptor-associated kinases (IRAKs), activation of mitogen-activated protein kinases (MAPKs) and NF-κB, and production of TNF-α were assessed by flow cytometry, western blotting, and enzyme-linked immunosorbent assay (ELISA), respectively. Our results showed that pretreatment with GA protected mice against LPS/D-GalN-induced fulminant hepatic failure (FHF), including a dose-dependent alleviation of mortality and ALT/AST elevation, ameliorating hepatic pathological damage, and decreasing TNF-α release. Moreover, GA inhibited LPS-induced activation of MAPKs and NF-κB in response to LPS, but the expression of TLR4 was not affected in vivo and in vitro. Notably, GA pretreatment in vivo suppressed IRAK-1 activity while inducing IRAK-M expression. Silencing of IRAK-M expression with siRNA blocked these beneficial effects of GA on the activation of MAPKs and NF-κB as well as TNF-α production in LPS-primed macrophages. Taken together, we conclude that GA could prevent LPS/D-GalN-induced FHF. The underlying mechanisms may be related to up-regulation of IRAK-M, which in turn caused deactivation of IRAK-1 and subsequent MAPKs and NF-κB, resulting in inhibiting TNF-α production. - Highlights: • Glycyrrhetinic acid protected from LPS/D-GalN-induced liver injury in mice. • Glycyrrhetinic acid inhibited LPS-induced TNF-α production in vivo and in vitro. • Glycyrrhetinic

  11. The Protective Effects of the Supercritical-Carbon Dioxide Fluid Extract of Chrysanthemum indicum against Lipopolysaccharide-Induced Acute Lung Injury in Mice via Modulating Toll-Like Receptor 4 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xiao-Li Wu

    2014-01-01

    Full Text Available The supercritical-carbon dioxide fluid extract of Chrysanthemum indicum Linné. (CFE has been demonstrated to be effective in suppressing inflammation. The aim of this study is to investigate the preventive action and underlying mechanisms of CFE on acute lung injury (ALI induced by lipopolysaccharide (LPS in mice. ALI was induced by intratracheal instillation of LPS into lung, and dexamethasone was used as a positive control. Results revealed that pretreatment with CFE abated LPS-induced lung histopathologic changes, reduced the wet/dry ratio and proinflammatory cytokines productions (TNF-α, IL-1β, and IL-6, inhibited inflammatory cells migrations and protein leakages, suppressed the levels of MPO and MDA, and upregulated the abilities of antioxidative enzymes (SOD, CAT, and GPx. Furthermore, the pretreatment with CFE downregulated the activations of NF-κB and the expressions of TLR4/MyD88. These results suggested that CFE exerted potential protective effects against LPS-induced ALI in mice and was a potential therapeutic drug for ALI. Its mechanisms were at least partially associated with the modulations of TLR4 signaling pathways.

  12. A Standardized Traditional Chinese Medicine Preparation Named Yejuhua Capsule Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Mice via Downregulating Toll-Like Receptor 4/Nuclear Factor-κB

    Directory of Open Access Journals (Sweden)

    Chu-Wen Li

    2015-01-01

    Full Text Available A standardized traditional Chinese medicine preparation named Yejuhua capsule (YJH has been clinically used in treatments of various acute respiratory system diseases with high efficacy and low toxicity. In this study, we were aiming to evaluate potential effects and to elucidate underlying mechanisms of YJH against lipopolysaccharide- (LPS- induced acute lung injury (ALI in mice. Moreover, the chemical analysis and chromatographic fingerprint study were performed for quality evaluation and control of this drug. ALI was induced by intratracheal instillation of LPS (5 mg/kg into the lung in mice and dexamethasone (5 mg/kg, p.o. was used as a positive control drug. Results demonstrated that pretreatments with YJH (85, 170, and 340 mg/kg, p.o. effectively abated LPS-induced histopathologic changes, attenuated the vascular permeability enhancement and edema, inhibited inflammatory cells migrations and protein leakages, suppressed the ability of myeloperoxidase, declined proinflammatory cytokines productions, and downregulated activations of nuclear factor-κB (NF-κB and expressions of toll-like receptor 4 (TLR4. This study demonstrated that YJH exerted potential protective effects against LPS-induced ALI in mice and supported that YJH was a potential therapeutic drug for ALI in clinic. And its mechanisms were at least partially associated with downregulations of TLR4/NF-κB pathways.

  13. Agomelatine, a MT1/MT2 melatonergic receptor agonist with serotonin 5-HT2C receptor antagonistic properties, suppresses Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    Science.gov (United States)

    Hyeon, Jin-Yi; Choi, Eun-Young; Choe, So-Hui; Park, Hae Ryoun; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2017-10-01

    This study was performed in an attempt to examine the influence of agomelatine in mitigating the generation of proinflammatory mediators in RAW264.7 murine macrophages exposed to lipopolysaccharide (LPS) obtained from Prevotella intermedia, a gram-negative anaerobic bacterium that is related with various types of periodontal diseases, and the molecular mechanisms behind its effects. LPS from P. intermedia strain ATCC 25611 was prepared employing the conventional phenol-water procedure. Conditioned culture media were analyzed for the levels of nitric oxide (NO), interleukin-1β (IL-1β) and IL-6. Real-time PCR analysis was carried out to determine the mRNA levels of inducible NO synthase (iNOS), IL-1β, IL-6 and SOCS1. Protein expression levels were evaluated by immunoblot test. NF-κB-dependent SEAP reporter assay was performed using a reporter cell line. DNA-binding activities of NF-κB subunits were analyzed utilizing the ELISA-based kits. Agomelatine was found to down-regulate significantly the generation of iNOS-derived NO, IL-1β and IL-6 as well as the expression of their mRNAs in cells activated with P. intermedia LPS. Agomelatine decreased NF-κB-dependent SEAP release caused by P. intermedia LPS. Agomelatine did not inhibit NF-κB transcription induced by LPS at the level of IκB-α degradation. Instead, LPS-induced nuclear translocation and DNA binding of NF-κB p50 subunit was blocked by agomelatine. P. intermedia LPS-elicited activation of STAT1 and STAT3 was reduced notably by co-treatment with agomelatine. Agomelatine showed a tendency to enhance mRNA level of SOCS1 in LPS-activated cells as well. Agomelatine merits further evaluation to reveal its usefulness on the host modulation of periodontal disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. The protective effect of lidocaine on lipopolysaccharide-induced acute lung injury in rats through NF-κB and p38 MAPK signaling pathway and excessive inflammatory responses.

    Science.gov (United States)

    Chen, L-J; Ding, Y-B; Ma, P-L; Jiang, S-H; Li, K-Z; Li, A-Z; Li, M-C; Shi, C-X; Du, J; Zhou, H-D

    2018-04-01

    Acute lung injury is a severe disease with a high rate of mortality, leading to more important illness. We aimed at exploring the protective role and potential mechanisms of lidocaine on lipopolysaccharide (LPS)-induced acute lung injury (ALI). Sprague Dawley (SD) rats were randomly assigned to control group receiving 0.9% saline solution, LPS group treated with 4 mg/kg LPS i.p., LPS + lidocaine(treated with 4 mg/kg LPS i.p. followed by giving 1 mg/kg, 3 mg/kg, 5 mg/kg of lidocaine i.v.). Lung specimens and the bronchoalveolar lavage fluid (BALF) were collected for histopathological examination and biochemical analyze 12 h after LPS induction. The cytokines expression of TNF-α, IL-6 and MCP-1 was measured by ELISA. In addition, the malondialdehyde (MDA) content, the activities of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in lung tissues were also detected using ELISA. The protein expressions of p38, p-p38, p65, p-p65 and IκB were analyzed by Western blot. The results indicated that after lidocaine treatment was able to decrease significantly wet-to-dry (W/D) ratio and ameliorate the histopathologic damage. Additionally, total protein content and the number of leukocytes in BALF significantly decreased. ELISA result indicated that the levels of TNF-α, IL-6 and MCP-1 in BALF were markedly suppressed. Meanwhile, the activities of T-AOC and SOD in lung tissues significantly increased, while the content of MDA significantly decreased after treatment with lidocaine. Moreover, Western blot suggested that lidocaine inhibited phosphorylation of NF-κB p65 and p38 MAPK. Therefore, lidocaine could ameliorate the LPS-induced lung injury via NF-κB/p38 MAPK signaling and excessive inflammatory responses, providing a potential for becoming the anti-inflammatory agent against lung injury.

  15. Ebselen Is a Potential Anti-Osteoporosis Agent by Suppressing Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclast Differentiation In vitro and Lipopolysaccharide-Induced Inflammatory Bone Destruction In vivo.

    Science.gov (United States)

    Baek, Jong Min; Kim, Ju-Young; Yoon, Kwon-Ha; Oh, Jaemin; Lee, Myeung Su

    2016-01-01

    Ebselen is a non-toxic seleno-organic drug with anti-inflammatory and antioxidant properties that is currently being examined in clinical trials to prevent and treat various diseases, including atherosclerosis, stroke, and cancer. However, no reports are available for verifying the pharmacological effects of ebselen on major metabolic bone diseases such as osteoporosis. In this study, we observed that ebselen suppressed the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in an osteoblast/osteoclast co-culture by regulating the ratio of receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin secreted by osteoblasts. In addition, ebselen treatment in the early stage of osteoclast differentiation inhibited RANKL-dependent osteoclastogenesis by decreasing the phosphorylation of IκB, PI3K, and Akt in early signaling pathways and by subsequently inducing c-Fos and nuclear factor of activated T-cells c1. Further, ebselen induced apoptosis of osteoclasts in the late stage of osteoclast differentiation. In addition, ebselen treatment suppressed filamentous actin ring formation and bone resorption activity of mature osteoclasts. Reflecting these in vitro effects, administration of ebselen recovered bone loss and its µ-CT parameters in lipopolysaccharide-mediated mouse model. Histological analysis confirmed that ebselen prevented trabecular bone matrix degradation and osteoclast formation in the bone tissues. Finally, it was proved that the anti-osteoclastogenic action of ebselen is achieved through targeting N-methyl-D-aspartate (NMDA) receptor. These results indicate that ebselen is a potentially safe drug for treating metabolic bone diseases such as osteoporosis.

  16. Effects of lidocaine on lipopolysaccharide-induced synovitis in horses Efeitos da lidocaína em sinovite induzida por lipopolissacarídeo, em eqüinos

    Directory of Open Access Journals (Sweden)

    R.C. Campebell

    2004-06-01

    Full Text Available Lidocaine (100mg 2% injected into the carpal joint was used to evaluate the inflammatory response induced by injection (1.5ng of intra-articular E. coli lipopolysaccharide (LPS endotoxin. Seventeen male Mangalarga horses aged two to three years were divided into three groups and in all animals was injected 0.9% saline (SAL in the left carpus (LC, and in the right carpus (RC one of the following combinations were injected: group A (n=6 LPS plus SAL; group B (n=6 LPS plus lidocaine; group C (n=5 lidocaine plus SAL. Synovial fluid and blood samples were collected immediately before the injection of LPS (T0, and at 1.5 (T1, 3 (T2, 6 (T3, 12 (T4 and 36 hours (T5 after the injection. Clinical and physical variables and cellular and biochemical characteristics of the synovial fluid were evaluated at the same time. The local and systemic inflammatory response was evaluated by measurement of mean serum and synovial fluid TNF-alpha concentration. A rise in TNF-alpha concentration in LPS injected joints at 3h in group A and from 1.5h to 3h in group B was observed. It is concluded that LPS triggered an inflammatory process and that lidocaine did not inhibit or attenuate the LPS-induced synovitis nor the synthesis and release of TNF-alpha .Injetou-se lidocaína (100mg 2% na articulação do carpo para avaliar a resposta inflamatória induzida pela injeção (1,5ng intra-articular de lipopolissacarídeo (LPS de E. coli. Utilizaram-se 17 cavalos Mangalarga não castrados, entre dois e três anos, divididos em três grupos. No carpo esquerdo (CE administrou-se solução fisiológica a 0,9% (SAL e no carpo direito (CD uma das seguintes combinações: grupo A (n=6 LPS mais SAL, grupo B (n=6 LPS mais lidocaína e grupo C (n=5 lidocaína mais SAL. Amostras do líquido sinovial e de sangue foram colhidas imediatamente antes da injeção de LPS (T0 e às 1,30 (T1, 3 (T2, 6 (T3, 12 (T4 e 36 horas (T5 após a injeção. Variáveis clínicas e físicas, e caracter

  17. Effects of lidocaine on lipopolysaccharide-induced synovitis in horses

    OpenAIRE

    Campebell,R.C.; Peiró,J.R.; Valadão,C.A.A.; Santana,A.E.; Cunha,F.Q.

    2004-01-01

    Lidocaine (100mg 2%) injected into the carpal joint was used to evaluate the inflammatory response induced by injection (1.5ng) of intra-articular E. coli lipopolysaccharide (LPS) endotoxin. Seventeen male Mangalarga horses aged two to three years were divided into three groups and in all animals was injected 0.9% saline (SAL) in the left carpus (LC), and in the right carpus (RC) one of the following combinations were injected: group A (n=6) LPS plus SAL; group B (n=6) LPS plus lidocaine; gro...

  18. Allicin Protects against Lipopolysaccharide-Induced Acute Lung ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of allicin, an active component of garlic, on lipopolysaccharide (LPS)- induced acute lung injury. Methods: Wistar rats were subjected to LPS intravenous injection with or without allicin treatment to induce acute lung injury (ALI) model. Also, A549 cells were stimulated with LPS in the ...

  19. Lipopolysaccharide induces amyloid formation of antimicrobial peptide HAL-2.

    Science.gov (United States)

    Wang, Jiarong; Li, Yan; Wang, Xiaoming; Chen, Wei; Sun, Hongbin; Wang, Junfeng

    2014-11-01

    Lipopolysaccharide (LPS), the important component of the outer membrane of Gram-negative bacteria, contributes to the integrity of the outer membrane and protects the cell against bactericidal agents, including antimicrobial peptides. However, the mechanisms of interaction between antimicrobial peptides and LPS are not clearly understood. Halictines-2 (HAL-2), one of the novel antimicrobial peptides, was isolated from the venom of the eusocial bee Halictus sexcinctus. HAL-2 has exhibited potent antimicrobial activity against Gram-positive and Gram-negative bacteria and even against cancer cells. Here, we studied the interactions between HAL-2 and LPS to elucidate the antibacterial mechanism of HAL-2 in vitro. Our results show that HAL-2 adopts a significant degree of β-strand structure in the presence of LPS. LPS is capable of inducing HAL-2 amyloid formation, which may play a vital role in its antimicrobial activity. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment.

    Science.gov (United States)

    Vasconcelos, Andrea R; Yshii, Lidia M; Viel, Tania A; Buck, Hudson S; Mattson, Mark P; Scavone, Cristoforo; Kawamoto, Elisa M

    2014-05-06

    Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses. Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1β and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1β, IFN-γ, RANTES, TNF-α and IL-6 levels. Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.

  1. Riboflavin attenuates lipopolysaccharide-induced lung injury in rats.

    Science.gov (United States)

    Al-Harbi, Naif O; Imam, Faisal; Nadeem, Ahmed; Al-Harbi, Mohammed M; Korashy, Hesham M; Sayed-Ahmed, Mohammed M; Hafez, Mohamed M; Al-Shabanah, Othman A; Nagi, Mahmoud N; Bahashwan, Saleh

    2015-01-01

    Riboflavin (vitamin B2) is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is therefore required by all flavoproteins. Riboflavin also works as an antioxidant by scavenging free radicals. The present study was designed to evaluate the effects of riboflavin against acute lungs injury induced by the administration of a single intranasal dose (20 μg/rat) of lipopolysaccharides (LPS) in experimental rats. Administration of LPS resulted in marked increase in malondialdehyde (MDA) level (p riboflavin in a dose-dependent manner (30 and 100 mg/kg, respectively). Riboflavin (100 mg/kg, p.o.) showed similar protective effects as dexamethasone (1 mg/kg, p.o.). Administration of LPS showed marked cellular changes including interstitial edema, hemorrhage, infiltration of PMNs, etc., which were reversed by riboflavin administration. Histopathological examinations showed normal morphological structures of lungs tissue in the control group. These biochemical and histopathological examination were appended with iNOS and CAT gene expression. The iNOS mRNA expression was increased significantly (p riboflavin significantly (p riboflavin caused a protective effect against LPS-induced ALI. These results suggest that riboflavin may be used to protect against toxic effect of LPS in lungs.

  2. RNA interference prevents lipopolysaccharide-induced preprotachykinin gene expression

    International Nuclear Information System (INIS)

    Lai, Y.-L.; Yu, S.C.; Chen, M.-J.

    2003-01-01

    We showed previously that lipopolysaccharide (LPS) induces noncholinergic airway hyperreactivity to capsaicin via an upregulation of tachykinin synthesis. This study was designed to test whether double-stranded preprotachykinin (ds PPT) RNA, RNA interference (RNAi), prevents the LPS-induced alterations. First, cultured primary nodose ganglial cells of newborn Brown-Norway rats were divided into four groups: control; LPS; LPS+RNAi; and LPS+RNAi+liposome. Second, young Brown-Norway rats for the in vivo study were divided into three groups (control; LPS; and LPS+RNAi), and ds PPT RNA was microinjected bilaterally into the nodose ganglia in the LPS+RNAi group. Then, ganglial cells were collected from the culture whereas the nodose ganglia and lungs were sampled from the animals, and PPT mRNA and substance P (SP) levels were analyzed. Also, airway reactivity to capsaicin was performed in vivo. LPS induced significant increases in PPT mRNA and SP levels in vitro and in vivo and an increase in airway reactivity to capsaicin in vivo. However, ds PPT RNA, but not scrambled RNA, prevented all LPS-induced alterations. The effect of ds PPT RNA was not enhanced by liposome in vitro. Therefore, we demonstrated that the local application of RNAi prevents effectively the activation of the noncholinergic system modulating the lungs/airways

  3. Minocycline protects against lipopolysaccharide-induced cognitive impairment in mice.

    Science.gov (United States)

    Hou, Yue; Xie, Guanbo; Liu, Xia; Li, Guoxun; Jia, Congcong; Xu, Jinghua; Wang, Bing

    2016-03-01

    The role of glial cells, especially microglia and astrocytes, in neuroinflammation and cognition has been studied intensively. Lipopolysaccharide (LPS), a commonly used inducer of neuroinflammation, can cause cognitive impairment. Minocycline is known to possess potent neuroprotective activity, but its effect on LPS-induced cognitive impairment is unknown. This study aims to investigate the effects of minocycline on LPS-induced cognitive impairment and glial cell activation in mice. Behavioral tests were conducted for cognitive function, immunohistochemistry for microglial and astrocyte response, and quantitative PCR for mRNA expression of proinflammatory cytokines. Minocycline significantly reversed the decreased spontaneous alternation induced by intrahippocampal administration of LPS in the Y-maze task. In the Morris water maze place navigation test, minocycline decreased the escape latency and distance traveled compared to LPS-treated mice. In the probe test, minocycline-treated mice spent more time in the target quadrant and crossed the platform area more frequently than animals in the LPS-treated group. Minocycline produced a significant decrease in the number of Iba-1- and GFAP-positive hippocampal cells compared to the LPS-treated group. Minocycline-treated mice had significantly reduced hippocampal TNF-α and IL-1β mRNA levels compared with LPS-treated animals. Minocycline caused a significant increase in hippocampal BDNF expression compared to the LPS-treated group. Minocycline can attenuate LPS-induced cognitive impairments in mice. This effect may be associated with its action to suppress the activation of microglia and astrocytes and to normalize BDNF expression. Since neuroinflammatory processes and cognitive impairments are implicated in neurodegenerative disorders, minocycline may be a promising candidate for treating such diseases.

  4. Dexmedetomidine reduces lipopolysaccharide induced neuroinflammation, sickness behavior, and anhedonia.

    Directory of Open Access Journals (Sweden)

    Ching-Hua Yeh

    Full Text Available Peripheral innate immune response may induce sickness behavior through activating microglia, excessive cytokines production, and neuroinflammation. Dexmedetomidine (Dex has anti-inflammatory effect. We investigated the effects of Dex on lipopolysaccharide (LPS-induced neuroinflammation and sickness behavior in mice.BALB/c mice were intraperitoneally (i.p. injected with Dex (50 ug/kg or vehicle. One hour later, the mice were injected (i.p. with Escherichia coli LPS (0.33 mg/kg or saline (n = 6 in each group. We analyzed the food and water intake, body weight loss, and sucrose preference of the mice for 24h. We also determined microglia activation and cytokines expression in the brains of the mice. In vitro, we determine cytokines expression in LPS-treated BV-2 microglial cells with or without Dex treatment.In the Dex-pretreated mice, LPS-induced sickness behavior (anorexia, weight loss, and social withdrawal were attenuated and microglial activation was lower than vehicle control. The mRNA expression of TNF-α, MCP-1, indoleamine 2, 3 dioxygenase (IDO, caspase-3, and iNOS were increased in the brain of LPS-challenged mice, which were reduced by Dex but not vehicle.Dexmedetomidine diminished LPS-induced neuroinflammation in the mouse brain and modulated the cytokine-associated changes in sickness behavior.

  5. Evidence for lipopolysaccharide-induced differentiation of RAW264 ...

    Indian Academy of Sciences (India)

    Unknown

    2Analytical Services Branch, HELD, National Institute for Occupational Safety and Health,. Center of Disease ... cells increased in cell size and acquired distinct dendritic morphology. ..... ferentiation of macrophages into DCs, further work is.

  6. Sirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysaccharide-stimulated macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Claudia A. [Universite catholique de Louvain, Louvain Drug Research Institute (LDRI), Pharmaceutics and Drug Delivery Research Group, Brussels B-1200 (Belgium); Fievez, Laurence [University of Liege, GIGA-Research, Laboratory of Cellular and Molecular Immunology, Liege B-4000 (Belgium); Neyrinck, Audrey M.; Delzenne, Nathalie M. [Universite catholique de Louvain, LDRI, Metabolism and Nutrition Research Group, Brussels B-1200 (Belgium); Bureau, Fabrice [University of Liege, GIGA-Research, Laboratory of Cellular and Molecular Immunology, Liege B-4000 (Belgium); Vanbever, Rita, E-mail: rita.vanbever@uclouvain.be [Universite catholique de Louvain, Louvain Drug Research Institute (LDRI), Pharmaceutics and Drug Delivery Research Group, Brussels B-1200 (Belgium)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer Lipopolysaccharide-stimulated macrophages were treated with cambinol and sirtinol. Black-Right-Pointing-Pointer Cambinol and sirtinol decreased lipopolysaccharide-induced cytokines. Black-Right-Pointing-Pointer Cambinol decreased NF-{kappa}B activity but had no impact on p38 MAPK activation. Black-Right-Pointing-Pointer Sirtuins are an interesting target for the treatment of inflammatory diseases. -- Abstract: In several inflammatory conditions such as rheumatoid arthritis or sepsis, the regulatory mechanisms of inflammation are inefficient and the excessive inflammatory response leads to damage to the host. Sirtuins are class III histone deacetylases that modulate the activity of several transcription factors that are implicated in immune responses. In this study, we evaluated the impact of sirtuin inhibition on the activation of lipopolysaccharide (LPS)-stimulated J774 macrophages by assessing the production of inflammatory cytokines. The pharmacologic inhibition of sirtuins decreased the production of tumour necrosis factor-alpha (TNF-{alpha}) interleukin 6 (IL-6) and Rantes. The reduction of cytokine production was associated with decreased nuclear factor kappa B (NF-{kappa}B) activity and inhibitor kappa B alpha (I{kappa}B{alpha}) phosphorylation while no impact was observed on the phosphorylation status of p38 mitogen-activated kinase (p38 MAPK). This work shows that sirtuin pharmacologic inhibitors are a promising tool for the treatment of inflammatory conditions.

  7. Sirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysaccharide-stimulated macrophages

    International Nuclear Information System (INIS)

    Fernandes, Cláudia A.; Fievez, Laurence; Neyrinck, Audrey M.; Delzenne, Nathalie M.; Bureau, Fabrice; Vanbever, Rita

    2012-01-01

    Highlights: ► Lipopolysaccharide-stimulated macrophages were treated with cambinol and sirtinol. ► Cambinol and sirtinol decreased lipopolysaccharide-induced cytokines. ► Cambinol decreased NF-κB activity but had no impact on p38 MAPK activation. ► Sirtuins are an interesting target for the treatment of inflammatory diseases. -- Abstract: In several inflammatory conditions such as rheumatoid arthritis or sepsis, the regulatory mechanisms of inflammation are inefficient and the excessive inflammatory response leads to damage to the host. Sirtuins are class III histone deacetylases that modulate the activity of several transcription factors that are implicated in immune responses. In this study, we evaluated the impact of sirtuin inhibition on the activation of lipopolysaccharide (LPS)-stimulated J774 macrophages by assessing the production of inflammatory cytokines. The pharmacologic inhibition of sirtuins decreased the production of tumour necrosis factor-alpha (TNF-α) interleukin 6 (IL-6) and Rantes. The reduction of cytokine production was associated with decreased nuclear factor kappa B (NF-κB) activity and inhibitor kappa B alpha (IκBα) phosphorylation while no impact was observed on the phosphorylation status of p38 mitogen-activated kinase (p38 MAPK). This work shows that sirtuin pharmacologic inhibitors are a promising tool for the treatment of inflammatory conditions.

  8. Broadleaf Mahonia attenuates granulomatous lobular mastitis-associated inflammation by inhibiting CCL-5 expression in macrophages

    Science.gov (United States)

    Wang, Zhiyu; Wang, Neng; Liu, Xiaoyan; Wang, Qi; Xu, Biao; Liu, Pengxi; Zhu, Huayu; Chen, Jianping; Situ, Honglin; Lin, Yi

    2018-01-01

    Granulomatous lobular mastitis (GLM) is a type of chronic mammary inflammation with unclear etiology. Currently systematic corticosteroids and methitrexate are considered as the main drugs for GLM treatment, but a high toxicity and risk of recurrence greatly limit their application. It is therefore an urgent requirement that safe and efficient natural drugs are found to improve the GLM prognosis. Broadleaf Mahonia (BM) is a traditional Chinese herb that is believed to have anti-inflammatory properties according to ancient records of traditional Chinese medicine. The present study investigated this belief and demonstrated that BM significantly inhibited the expression of interleukin-1β (IL-1β), IL-6, cyclooxygenase-2 and inducible nitric oxide synthase in RAW264.7 cells, but had little influence on the cell viability, cell cycle and apoptosis. Meanwhile, the lipopolysaccharide-induced elevation of reactive oxygen species and nitric oxide was also blocked following BM treatment, accompanied with decreased activity of nuclear factor-κB and MAPK signaling. A cytokine array further validated that BM exhibited significant inhibitory effects on several chemoattractants, including chemokine (C-C motif) ligand (CCL)-2, CCL-3, CCL-5 and secreted tumor necrosis factor receptor 1, among which CCL-5 exhibited the highest inhibition ratio in cell and clinical GLM specimens. Collectively, the results show that BM is a novel effective anti-inflammatory herb in vitro and ex vivo, and that CCL-5 may be closely associated with GLM pathogenesis. PMID:29138800

  9. Wastes options

    International Nuclear Information System (INIS)

    Maes, M.

    1992-01-01

    After a description of the EEC environmental policy, some wastes families are described: bio-contaminant wastes (municipal and industrial), hospitals wastes, toxic wastes in dispersed quantities, nuclear wastes (radioactive and thermal), plastics compounds wastes, volatiles organic compounds, hydrocarbons and used solvents. Sources, quantities and treatments are given. (A.B.). refs., figs., tabs

  10. Waste Sites - Municipal Waste Operations

    Data.gov (United States)

    NSGIC Education | GIS Inventory — A Municipal Waste Operation is a DEP primary facility type related to the Waste Management Municipal Waste Program. The sub-facility types related to Municipal Waste...

  11. Inhibition of the radiolytic hydrogen production in the nuclear waste of 'bitumen coated' type: study of the interaction between hydrogen and cobalt hydroxo-sulphide

    International Nuclear Information System (INIS)

    Pichon, C.

    2006-11-01

    In the nuclear field in France, the bitumen is mainly used for the conditioning of the radioactive muds generated by the fuel reprocessing. However, the self-irradiation of the bitumen induces a production of hydrogen which generates safety problems. The comparison of various storage sites showed that the presence of cobalt hydroxo sulphide limited such a production. Consequently, this compound was regarded as an 'inhibitor of radiolytic hydrogen production'. However, the origin of this phenomenon was not clearly identified. In order to propose an explanation to this inhibition phenomenon, model organic molecules were used to represent the components of the bitumen. Irradiations were carried out by protons to simulate the alpha radiolysis. The organic molecules irradiations by a proton beam showed that cobalt hydroxo sulphide CoSOH, does not act as a hydrogenation catalyst of unsaturated hydrocarbons, nor as a radicals scavenger, but consists of a trap of hydrogen. Experiments of hydrogen trapping at ambient temperature were carried out according to two techniques: gravimetry and manometry. The solid was characterized before and after interaction with hydrogen (infrared and Raman spectroscopies, X-ray diffraction). The initial solid was composed of amorphous cobalt hydroxo sulphide and a minor phase of cobalt hydroxide. The gravimetry and manometry experiments showed that the maximum of hydrogen trapping capacity is equal to 0.59 ± 0.18 mole of hydrogen per mole of cobalt. After interaction with hydrogen, the Co(OH) 2 phase disappeared and a new solid phase appeared corresponding to Co 9 S 8 . These observations, as well as the analysis of the gas phase, made it possible to conclude with the following reaction (1): 9 CoSOH + 11/2 H 2 = Co 9 S 8 + 9 H 2 O + H 2 S (1). Gravimetry experiments at temperatures between 50 and 210 C revealed the desorption of water but not of hydrogen sulphide. The absence of hydrogen sulphide in gaseous phase and the Co(OH) 2 phase

  12. Solid waste

    International Nuclear Information System (INIS)

    1995-01-01

    The article drawn up within the framework of 'the assessment of the state of the environment in Lebanon' provides an overview of solid waste management, and assesses future wastes volume and waste disposal issues.In particular it addresses the following concerns: - Long term projections of solid waste arisings (i.e. domestic, industrial, such commercial wastes, vehicle types, construction waste, waste oils, hazardous toxic wastes and finally hospital and clinical wastes) are described. - Appropriate disposal routes, and strategies for reducing volumes for final disposal - Balance between municipal and industrial solid waste generation and disposal/treatment and - environmental impacts (aesthetics, human health, natural environment )of existing dumps, and the potential impact of government plans for construction of solid waste facilities). Possible policies for institutional reform within the waste management sector are proposed. Tables provides estimations of generation rates and distribution of wastes in different regions of Lebanon. Laws related to solid waste management are summarized

  13. Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Dong Ju Son

    2014-08-01

    Full Text Available PURPOSE: Piperine, a major alkaloid of black pepper (Piper nigrum and long pepper (Piper longum, was shown to have anti-inflammatory activity through the suppression of cyclooxygenase (COX-2 gene expression and enzyme activity. It is also reported to exhibit anti-platelet activity, but the mechanism underlying this action remains unknown. In this study, we investigated a putative anti-platelet aggregation mechanism involving arachidonic acid (AA metabolism and how this compares with the mechanism by which it inhibits macrophage inflammatory responses; METHODS: Rabbit platelets and murine macrophage RAW264.7 cells were treated with piperine, and the effect of piperine on the activity of AA-metabolizing enzymes, including cytosolic phospholipase A2 (cPLA2, COX-1, COX-2, and thromboxane A2 (TXA2 synthase, as well as its effect on AA liberation from the plasma membrane components, were assessed using isotopic labeling methods and enzyme immunoassay kit; RESULTS: Piperine significantly suppressed AA liberation by attenuating cPLA2 activity in collagen-stimulated platelets. It also significantly inhibited the activity of TXA2 synthase, but not of COX-1, in platelets. These results suggest that piperine inhibits platelet aggregation by attenuating cPLA2 and TXA2 synthase activities, rather than through the inhibition of COX-1 activity. On the other hand, piperine significantly inhibited lipopolysaccharide-induced generation of prostaglandin (PGE2 and PGD2 in RAW264.7 cells by suppressing the activity of COX-2, without effect on cPLA2; CONCLUSION: Our findings indicate that piperine inhibits platelet aggregation and macrophage inflammatory response by different mechanisms.

  14. TRAM-Derived Decoy Peptides inhibits the inflammatory response in mouse mammary epithelial cells and a mastitis model in mice.

    Science.gov (United States)

    Hu, Xiaoyu; Tian, Yuan; Wang, Tiancheng; Zhang, Wenlong; Wang, Wei; Gao, Xuejiao; Qu, Shihui; Cao, Yongguo; Zhang, Naisheng

    2015-10-05

    It has been proved that TRAM-Derived Decoy peptides have anti-inflammatory properties. In this study, we synthesized a TRAM-Derived decoy peptide (TM6), belongs to TRAM TIR domain, of which sequence is "N"-RQIKIWFQNRRMKWK, KENFLRDTWCNFQFY-"C" and evaluated the effects of TM6 on lipopolysaccharide-induced mastitis in mice. In vivo, LPS-induced mice mastitis model was established by injection of LPS through the duct of mammary gland. TM6 was injected 1h before or after LPS treatment. In vitro, primary mouse mammary epithelial cells were used to investigate the effects of TM6 on LPS-induced inflammatory responses. The results showed that TM6 inhibited LPS-induced mammary gland histopathologic changes, MPO activity, and TNF-α, IL-1β and IL-6 production in mice. In vitro, TM6 significantly inhibited LPS-induced TNF-α and IL-6 production, as well as NF-κB and MAPKs activation. In conclusion, this study demonstrated that TM6 had protective effects on LPS-mastitis and may be a promising therapeutic reagent for mastitis treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Electroacupuncture Improved Hippocampal Neurogenesis following Traumatic Brain Injury in Mice through Inhibition of TLR4 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yuqin Ye

    2017-01-01

    Full Text Available The protective role of electroacupuncture (EA treatment in diverse neurological diseases such as ischemic stroke is well acknowledged. However, whether and how EA act on hippocampal neurogenesis following traumatic brain injury (TBI remains poorly understood. This study aims to investigate the effect of EA on hippocampal neurogenesis and neurological functions, as well as its underlying association with toll-like receptor 4 (TLR4 signaling in TBI mice. BrdU/NeuN immunofluorescence was performed to label newborn neurons in the hippocampus after EA treatment. Water maze test and neurological severity score were used to evaluate neurological function posttrauma. The hippocampal level of TLR4 and downstream molecules and inflammatory cytokines were, respectively, detected by Western blot and enzyme-linked immunosorbent assay. EA enhanced hippocampal neurogenesis and inhibited TLR4 expression at 21, 28, and 35 days after TBI, but the beneficial effects of EA on posttraumatic neurogenesis and neurological functions were attenuated by lipopolysaccharide-induced TLR4 activation. In addition, EA exerted an inhibitory effect on both TLR4/Myd88/NF-κB and TLR4/TRIF/NF-κB pathways, as well as the inflammatory cytokine expression in the hippocampus following TBI. In conclusion, EA promoted hippocampal neurogenesis and neurological recovery through inhibition of TLR4 signaling pathway posttrauma, which may be a potential approach to improve the outcome of TBI.

  16. Waste management - sewage - special wastes

    International Nuclear Information System (INIS)

    1987-01-01

    The 27 papers represent a cross-section of the subject waste management. Particular attention is paid to the following themes: waste avoidance, waste product utilization, household wastes, dumping technology, sewage sludge treatments, special wastes, seepage from hazardous waste dumps, radioactive wastes, hospital wastes, purification of flue gas from waste combustion plants, flue gas purification and heavy metals, as well as combined sewage sludge and waste product utilization. The examples given relate to plants in Germany and other European countries. 12 papers have been separately recorded in the data base. (DG) [de

  17. Waste management

    International Nuclear Information System (INIS)

    Chmielewska, E.

    2010-01-01

    In this chapter formation of wastes and basic concepts of non-radioactive waste management are explained. This chapter consists of the following parts: People in Peril; Self-regulation of nature as a guide for minimizing and recycling waste; The current waste management situation in the Slovak Republic; Categorization and determination of the type of waste in legislative of Slovakia; Strategic directions waste management in the Slovak Republic.

  18. Corrosion inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, A O

    1965-12-29

    An acid corrosion-inhibiting composition consists essentially of a sugar, and an alkali metal salt selected from the group consisting of iodides and bromides. The weight ratio of the sugar to the alkali metal salt is between 2:1 and about 20,000:1. Also, a corrosion- inhibited phosphoric acid composition comprising at least about 20 wt% of phosphoric acid and between about 0.1 wt% and about 10 wt% of molasses, and between about 0.0005 wt% and about 1 wt% of potassium iodide. The weight ratio of molasses to iodide is greater than about 2:1. (11 claims)

  19. Radioactive wastes

    International Nuclear Information System (INIS)

    Grass, F.

    1982-01-01

    Following a definition of the term 'radioactive waste', including a discussion of possible criteria allowing a delimitation of low-level radioactive against inactive wastes, present techniques of handling high-level, intermediate-level and low-level wastes are described. The factors relevant for the establishment of definitive disposals for high-level wastes are discussed in some detail. Finally, the waste management organization currently operative in Austria is described. (G.G.)

  20. Antioxidant activity, inhibition of nitric oxide overproduction, and in vitro antiproliferative effect of maple sap and syrup from Acer saccharum.

    Science.gov (United States)

    Legault, Jean; Girard-Lalancette, Karl; Grenon, Carole; Dussault, Catherine; Pichette, André

    2010-04-01

    Antioxidant activity, inhibition of nitric oxide (NO) overproduction, and antiproliferative effect of ethyl acetate extracts of maple sap and syrup from 30 producers were evaluated in regard to the period of harvest in three different regions of Québec, Canada. Oxygen radical absorbance capacity (ORAC) values of maple sap and syrup extracts are, respectively, 12 +/- 6 and 15 +/- 5 micromol of Trolox equivalents (TE)/mg. The antioxidant activity was also confirmed by a cell-based assay. The period of harvest has no statistically significant incidence on the antioxidant activity of both extracts. The antioxidant activity of pure maple syrup was also determined using the ORAC assay. Results indicate that the ORAC value of pure maple syrup (8 +/- 2 micromol of TE/mL) is lower than the ORAC value of blueberry juice (24 +/- 1 micromol of TE/mL) but comparable to the ORAC values of strawberry (10.7 +/- 0.4 micromol of TE/mL) and orange (10.8 +/- 0.5 micromol of TE/mL) juices. Maple sap and syrup extracts showed to significantly inhibit lipopolysaccharide-induced NO overproduction in RAW264.7 murine macrophages. Maple syrup extract was significantly more active than maple sap extract, suggesting that the transformation of maple sap into syrup increases NO inhibition activity. The highest NO inhibition induced by the maple syrup extracts was observed at the end of the season. Moreover, darker maple syrup was found to be more active than clear maple syrup, suggesting that some colored oxidized compounds could be responsible in part for the activity. Finally, maple syrup extracts (50% inhibitory concentration = 42 +/- 6 microg/mL) and pure maple syrup possess a selective in vitro antiproliferative activity against cancer cells.

  1. Waste management, waste resource facilities and waste conversion processes

    International Nuclear Information System (INIS)

    Demirbas, Ayhan

    2011-01-01

    In this study, waste management concept, waste management system, biomass and bio-waste resources, waste classification, and waste management methods have been reviewed. Waste management is the collection, transport, processing, recycling or disposal, and monitoring of waste materials. A typical waste management system comprises collection, transportation, pre-treatment, processing, and final abatement of residues. The waste management system consists of the whole set of activities related to handling, treating, disposing or recycling the waste materials. General classification of wastes is difficult. Some of the most common sources of wastes are as follows: domestic wastes, commercial wastes, ashes, animal wastes, biomedical wastes, construction wastes, industrial solid wastes, sewer, biodegradable wastes, non-biodegradable wastes, and hazardous wastes.

  2. Conditioning of alpha bearing wastes

    International Nuclear Information System (INIS)

    1991-01-01

    Alpha bearing wastes are generated during the reprocessing of spent fuel, mixed oxide fuel fabrication, decommissioning and other activities. The safe and effective management of these wastes is of particular importance owing to the radiotoxicity and long lived characteristics of certain transuranic (TRU) elements. The management of alpha bearing wastes involves a number of stages which include collection, characterization, segregation, treatment, conditioning, transport, storage and disposal. This report describes the currently available matrices and technologies for the conditioning of alpha wastes and relates them to their compatibility with the other stages of the waste management process. The selection of a specific immobilization process is dependent on the waste treatment state and the subsequent handling, transport, storage and disposal requirements. The overall objectives of immobilization are similar for all waste producers and processors, which are to produce: (a) Waste forms with sufficient mechanical, physical and chemical stability to satisfy all stages of handling, transport and storage (referred to as the short term requirements), and (b) Waste forms which will satisfy disposal requirements and inhibit the release of radionuclides to the biosphere (referred to as the long term requirements). Cement and bitumen processes have already been successfully applied to alpha waste conditioning on the industrial scale in many of the IAEA Member States. Cement systems based on BFS and pozzolanic cements have emerged as the principal encapsulation matrices for the full range of alpha bearing wastes. Alternative technologies, such as polymers and ceramics, are being developed for specific waste streams but are unlikely to meet widespread application owing to cost and process complexity. The merits of alpha waste conditioning are improved performance in transport, storage and disposal combined with enhanced public perception of waste management operations. These

  3. Residential Waste

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund; Fruergaard, Thilde; Matsufuji, Y.

    2011-01-01

    are discussed in this chapter. Characterizing residential waste is faced with the problem that many residences already divert some waste away from the official collection systems, for example performing home composting of vegetable waste and garden waste, having their bundled newspaper picked up by the scouts...... twice a year or bringing their used furniture to the flea markets organized by charity clubs. Thus, much of the data available on residential waste represents collected waste and not necessarily all generated waste. The latter can only be characterized by careful studies directly at the source......, but such studies are very expensive if fair representation of both spatial and temporal variations should be obtained. In addition, onsite studies may affect the waste generation in the residence because of the increased focus on the issue. Residential waste is defined in different ways in different countries...

  4. Mining wastes

    International Nuclear Information System (INIS)

    Pradel, J.

    1981-01-01

    In this article mining wastes means wastes obtained during extraction and processing of uranium ores including production of uraniferous concentrates. The hazards for the population are irradiation, ingestion, dust or radon inhalation. The different wastes produced are reviewed. Management of liquid effluents, water treatment, contamined materials, gaseous wastes and tailings are examined. Environmental impact of wastes during and after exploitation is discussed. Monitoring and measurements are made to verify that ICRP recommendations are met. Studies in progress to improve mining waste management are given [fr

  5. Inhibition of methane production by Methanobacterium formicicum

    Energy Technology Data Exchange (ETDEWEB)

    Hobson, P N; Shaw, B G

    1976-01-01

    The effects of volatile fatty acids, ammonia and copper on methane production by growing cultures of Methanobacterium formicicum were studied. Acetate and butyrate were not inhibitory, but propionate was inhibitory above certain concentrations, as was ammonia. Copper was inhibitory, but inhibitory concentrations are difficult to define as varying amounts may be precipitated as the sulphide. The results are compared with those from piggery-waste digesters and it is suggested that failure of farm-waste digesters from such inhibitions is unlikely.

  6. Waste management

    DEFF Research Database (Denmark)

    Bruun Hansen, Karsten; Jamison, Andrew

    2000-01-01

    The case study deals with public accountability issues connected to household waste management in the municipality of Copenhagen, Denmark.......The case study deals with public accountability issues connected to household waste management in the municipality of Copenhagen, Denmark....

  7. Radioactive wastes

    International Nuclear Information System (INIS)

    Devarakonda, M.S.; Melvin, J.M.

    1994-01-01

    This paper is part of the Annual Literature Review issue of Water Environment Research. The review attempts to provide a concise summary of important water-related environmental science and engineering literature of the past year, of which 40 separate topics are discussed. On the topic of radioactive wastes, the present paper deals with the following aspects: national programs; waste repositories; mixed wastes; waste processing and decommissioning; environmental occurrence and transport of radionuclides; and remedial actions and treatment. 178 refs

  8. Waste disposal

    International Nuclear Information System (INIS)

    Neerdael, B.; Marivoet, J.; Put, M.; Verstricht, J.; Van Iseghem, P.; Buyens, M.

    1998-01-01

    The primary mission of the Waste Disposal programme at the Belgian Nuclear Research Centre SCK/CEN is to propose, develop, and assess solutions for the safe disposal of radioactive waste. In Belgium, deep geological burial in clay is the primary option for the disposal of High-Level Waste and spent nuclear fuel. The main achievements during 1997 in the following domains are described: performance assessment, characterization of the geosphere, characterization of the waste, migration processes, underground infrastructure

  9. Waste incineration

    International Nuclear Information System (INIS)

    Rumplmayr, A.; Sammer, G.

    2001-01-01

    Waste incineration can be defined as the thermal conversion processing of solid waste by chemical oxidation. The types of wastes range from solid household waste and infectious hospital waste through to toxic solid, liquid and gaseous chemical wastes. End products include hot incineration gases, composed primarily of nitrogen, carbon dioxide, water vapor and to a smaller extend of non-combustible residue (ash) and air pollutants (e. g. NO x ). Energy can be recovered by heat exchange from the hot incineration gases, thus lowering fossil fuel consumption that in turn can reduce emissions of greenhouse gases. Burning of solid waste can fulfil up to four distinctive objectives (Pera, 2000): 1. Volume reduction: volume reduction of about 90 %, weight reduction of about 70 %; 2. Stabilization of waste: oxidation of organic input; 3. Recovery of energy from waste; 4. Sanitization of waste: destruction of pathogens. Waste incineration is not a means to make waste disappear. It does entail emissions into air as well as water and soil. The generated solid residues are the topic of this task force. Unlike other industrial processes discussed in this platform, waste incineration is not a production process, and is therefore not generating by-products, only residues. Residues that are isolated from e. g. flue gas, are concentrated in another place and form (e. g. air pollution control residues). Hence, there are generally two groups of residues that have to be taken into consideration: residues generated in the actual incineration process and others generated in the flue gas cleaning system. Should waste incineration finally gain public acceptance, it will be necessary to find consistent regulations for both sorts of residues. In some countries waste incineration is seen as the best option for the treatment of waste, whereas in other countries it is seen very negative. (author)

  10. Radioactive Waste.

    Science.gov (United States)

    Blaylock, B. G.

    1978-01-01

    Presents a literature review of radioactive waste disposal, covering publications of 1976-77. Some of the studies included are: (1) high-level and long-lived wastes, and (2) release and burial of low-level wastes. A list of 42 references is also presented. (HM)

  11. Hazardous Waste

    Science.gov (United States)

    ... chemicals can still harm human health and the environment. When you throw these substances away, they become hazardous waste. Some hazardous wastes come from products in our homes. Our garbage can include such hazardous wastes as old batteries, bug spray cans and paint thinner. U.S. residents ...

  12. Waste treatment

    International Nuclear Information System (INIS)

    Hutson, G.V.

    1996-01-01

    Numerous types of waste are produced by the nuclear industry ranging from high-level radioactive and heat-generating, HLW, to very low-level, LLW and usually very bulky wastes. These may be in solid, liquid or gaseous phases and require different treatments. Waste management practices have evolved within commercial and environmental constraints resulting in considerable reduction in discharges. (UK)

  13. Nuclear wastes

    International Nuclear Information System (INIS)

    2004-01-01

    Here is made a general survey of the situation relative to radioactive wastes. The different kinds of radioactive wastes and the different way to store them are detailed. A comparative evaluation of the situation in France and in the world is made. The case of transport of radioactive wastes is tackled. (N.C.)

  14. Radioactive wastes

    International Nuclear Information System (INIS)

    Teillac, J.

    1988-01-01

    This study of general interest is an evaluation of the safety of radioactive waste management and consequently the preservation of the environment for the protection of man against ionizing radiations. The following topics were developed: radiation effects on man; radioactive waste inventory; radioactive waste processing, disposal and storage; the present state and future prospects [fr

  15. Electronic wastes

    Science.gov (United States)

    Regel-Rosocka, Magdalena

    2018-03-01

    E-waste amount is growing at about 4% annually, and has become the fastest growing waste stream in the industrialized world. Over 50 million tons of e-waste are produced globally each year, and some of them end up in landfills causing danger of toxic chemicals leakage over time. E-waste is also sent to developing countries where informal processing of waste electrical and electronic equipment (WEEE) causes serious health and pollution problems. A huge interest in recovery of valuable metals from WEEE is clearly visible in a great number of scientific, popular scientific publications or government and industrial reports.

  16. Ketamine inhibits transcription factors activator protein 1 and nuclear factor-kappaB, interleukin-8 production, as well as CD11b and CD16 expression: studies in human leukocytes and leukocytic cell lines.

    NARCIS (Netherlands)

    Welters, I.D.; Hafer, G.; Menzebach, A.; Muhling, J.; Neuhauser, C.; Browning, P.; Goumon, Y.

    2010-01-01

    BACKGROUND: Recent data indicate that ketamine exerts antiinflammatory actions. However, little is known about the signaling mechanisms involved in ketamine-induced immune modulation. In this study, we investigated the effects of ketamine on lipopolysaccharide-induced activation of transcription

  17. Plastic solidification method for radioactive waste

    International Nuclear Information System (INIS)

    Tomita, Toshihide; Inakuma, Masahiko.

    1992-01-01

    Condensed liquid wastes in radioactive wastes are formed by mixing and condensing several kinds of liquid wastes such as liquid wastes upon regeneration of ion exchange resins, floor draining liquid wastes and equipment draining liquid wastes. Accordingly, various materials are contained, and it is found that polymerization reaction of plastics is inhibited especially when reductive material, such as sodium nitrite is present. Then, in the present invention, upon mixing thermosetting resins to radioactive wastes containing reducing materials, an alkaline material is admixed to an unstaturated polyester resin. This can inactivate the terminal groups of unsaturated polyester chain, to prevent the dissociation of the reducing agent such as sodium nitrite. Further, if an unsaturated polyester resin of low acid value and a polymerization initiator for high temperature are used in addition to the alkaline material, the effect is further enhanced, thereby enabling to obtain a strong plastic solidification products. (T.M.)

  18. Discarding processing method for radioactive waste

    International Nuclear Information System (INIS)

    Komura, Shiro; Kato, Hiroaki; Hatakeyama, Takao; Oura, Masato.

    1992-01-01

    At first, in a discrimination step, extremely low level radioactive wastes are discriminated to metals and concretes and further, the metal wastes are discriminated to those having hollow portions and those not having hollow portions, and the concrete wastes are discriminated to those having block-like shape and those having other shapes respectively. Next, in a processing step, the metal wastes having hollow portions are applied with cutting, devoluming or packing treatment and block-like concrete wastes are applied with surface solidification treatment, and concrete wastes having other shapes are applied with crushing treatment respectively. Then, the extremely low level radioactive wastes contained in a container used exclusively for transportation are taken out, in a movable burying facility with diffusion inhibiter kept at a negative pressure as required, in a field for burying operation, and buried in a state that they are isolated from the outside. Accordingly, they can be buried safely and efficiently. (T.M.)

  19. Inhibition of Oncogenic Transcription Factor REL by the Natural Product Derivative Calafianin Monomer 101 Induces Proliferation Arrest and Apoptosis in Human B-Lymphoma Cell Lines.

    Science.gov (United States)

    Yeo, Alan T; Chennamadhavuni, Spandan; Whitty, Adrian; Porco, John A; Gilmore, Thomas D

    2015-04-23

    Increased activity of transcription factor NF-κB has been implicated in many B-cell lymphomas. We investigated effects of synthetic compound calafianin monomer (CM101) on biochemical and biological properties of NF-κB. In human 293 cells, CM101 selectively inhibited DNA binding by overexpressed NF-κB subunits REL (human c-Rel) and p65 as compared to NF-κB p50, and inhibition of REL and p65 DNA binding by CM101 required a conserved cysteine residue. CM101 also inhibited DNA binding by REL in human B-lymphoma cell lines, and the sensitivity of several B-lymphoma cell lines to CM101-induced proliferation arrest and apoptosis correlated with levels of cellular and nuclear REL. CM101 treatment induced both phosphorylation and decreased expression of anti-apoptotic protein Bcl-XL, a REL target gene product, in sensitive B-lymphoma cell lines. Ectopic expression of Bcl-XL protected SUDHL-2 B-lymphoma cells against CM101-induced apoptosis, and overexpression of a transforming mutant of REL decreased the sensitivity of BJAB B-lymphoma cells to CM101-induced apoptosis. Lipopolysaccharide-induced activation of NF-κB signaling upstream components occurred in RAW264.7 macrophages at CM101 concentrations that blocked NF-κB DNA binding. Direct inhibitors of REL may be useful for treating B-cell lymphomas in which REL is active, and may inhibit B-lymphoma cell growth at doses that do not affect some immune-related responses in normal cells.

  20. Waste -92

    International Nuclear Information System (INIS)

    Ekwall, K.

    1992-11-01

    The report gives a review of waste incineration in Sweden today, including environmental and legal aspects. 21 incinerator plants are in use, producing heat to district heating network and, to a minor part, electric power. In 1991 1.31 Mton household waste and 0.35 Mton industrial waste were incinerated producing 4.4 Twh of energy. In a few cities 30-40 percent of the district heat comes from waste incineration. The theoretical and practical potentials for energy production in Sweden are estimated to 7 respective 5 TWh for household waste and 9 respective 5-6 TWh for industrial waste. Landfill gas is extracted at about 35 sites, with a yearly production of 0.3 TWh which corresponds to 3-5 percent of the potentially recoverable quantity. (8 refs., 2 figs., 13 tabs.)

  1. Industrial Waste

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund

    2011-01-01

    generation rates and material composition as well as determining factors are discussed in this chapter. Characterizing industrial waste is faced with the problem that often only a part of the waste is handled in the municipal waste system, where information is easily accessible. In addition part...... of the industrial waste may in periods, depending on market opportunities and prices, be traded as secondary rawmaterials. Production-specificwaste from primary production, for example steel slag, is not included in the current presentation. In some countries industries must be approved or licensed and as part...... of the system industry has to inform at the planning stage and afterwards in yearly reports on their waste arising and how the waste is managed. If available such information is very helpful in obtaining information about that specific industry. However, in many countries there is very little information...

  2. Nuclear waste

    International Nuclear Information System (INIS)

    1990-01-01

    Each year, nuclear power plants, businesses, hospitals, and universities generate more than 1 million cubic feet of hardware, rags, paper, liquid waste, and protective clothing that have been contaminated with radioactivity. While most of this waste has been disposed of in facilities in Nevada, South Carolina, and Washington state, recent legislation made the states responsible - either individually, or through groups of states called compacts - for developing new disposal facilities. This paper discusses the states' progress and problems in meeting facility development milestones in the law, federal and state efforts to resolve issues related to mixed waste (low-level waste that also contains hazardous chemicals) and waste with very low levels of radioactivity, and the Department of Energy's progress in discharging the federal government's responsibility under the law to manage the most hazardous low-level waste

  3. Waste indicators

    Energy Technology Data Exchange (ETDEWEB)

    Dall, O.; Lassen, C.; Hansen, E. [Cowi A/S, Lyngby (Denmark)

    2003-07-01

    The Waste Indicator Project focuses on methods to evaluate the efficiency of waste management. The project proposes the use of three indicators for resource consumption, primary energy and landfill requirements, based on the life-cycle principles applied in the EDIP Project. Trial runs are made With the indicators on paper, glass packaging and aluminium, and two models are identified for mapping the Danish waste management, of which the least extensive focuses on real and potential savings. (au)

  4. Waste indicators

    International Nuclear Information System (INIS)

    Dall, O.; Lassen, C.; Hansen, E.

    2003-01-01

    The Waste Indicator Project focuses on methods to evaluate the efficiency of waste management. The project proposes the use of three indicators for resource consumption, primary energy and landfill requirements, based on the life-cycle principles applied in the EDIP Project. Trial runs are made With the indicators on paper, glass packaging and aluminium, and two models are identified for mapping the Danish waste management, of which the least extensive focuses on real and potential savings. (au)

  5. Wasting away

    International Nuclear Information System (INIS)

    Salzman, L.

    1978-01-01

    The problems of radioactive waste disposal are discussed, with particular reference to the following: radiation hazards from uranium mill tailings; disposal and storage of high-level wastes from spent fuel elements and reprocessing; low-level wastes; decommissioning of aged reactors; underground disposal, such as in salt formations; migration of radioactive isotopes, for example into ground water supplies or into the human food chain. (U.K.)

  6. Waste Incinerator

    International Nuclear Information System (INIS)

    1994-05-01

    This book deals with plan and design of waste incinerator, which includes process outline of waste, method of measure, test, analysis, combustion way and classification of incineration facilities, condition of combustion and incineration, combustion calculation and heat calculation, ventilation and flow resistivity, an old body and component materials of supplementary installation, attached device, protection of pollution of incineration ash and waste gas, deodorization, prevention of noise in incineration facility, using heat and electric heat, check order of incineration plan.

  7. Waste Management

    OpenAIRE

    Anonymous

    2006-01-01

    The Productivity Commission’s inquiry report into ‘Waste Management’ was tabled by Government in December 2006. The Australian Government asked the Commission to identify policies that would enable Australia to address market failures and externalities associated with the generation and disposal of waste, and recommend how resource efficiencies can be optimised to improve economic, environmental and social outcomes. In the final report, the Commission maintains that waste management policy sh...

  8. Disposal method of radioactive wastes

    International Nuclear Information System (INIS)

    Uetake, Naoto; Fukazawa, Tetsuo.

    1986-01-01

    Purpose: To improve the safety of underground disposal of radioactive wastes for a long period of time by surrounding the periphery of the radioactive wastes with materials that can inhibit the migration of radioactive nuclides and are physically and chemically stable. Method: Hardening products prepared from a water-hardenable calcium silicate compound and an aqueous solution of alkali silicate have compression strength as comparable with that of concretes, high water tightness and adsorbing property to radioactive isotopes such as cobalt similar to that of concretes and they also show adsorption to cesium which is not adsorbed to concretes. Further, the kneaded slurry thereof is excellent in the workability and can be poured even into narrow gaps. Accordingly, by alternately charging granular radioactive wastes and this slurry before hardening into the ground, the radioactive wastes can be put to underground disposal stably with simple procedures. (Kamimura, M.)

  9. Recycling waste

    Energy Technology Data Exchange (ETDEWEB)

    Smith, P I.S.

    1976-01-01

    It is being realized that if environmental quality is to be improved the amount of waste generated by man has to be substantially reduced. There are two ways this can be achieved. First, by conserving materials and energy, and sacrificing economic growth, a solution that is completely unacceptable because it would mean some form of rationing, mass unemployment, and collapse of society as it is known. The second way to reduce the volume of waste is by planned recycling, re-use, and recovery. Already the reclamation industry recovers, processes, and turns back for re-use many products used by industry and thereby reduces the UK's import bill for raw materials. In the book, the author sets out the various ways materials may be recovered from industrial and municipal wastes. The broad technology of waste management is covered and attention is focused on man's new resources lying buried in the mountains of industrial wastes, the emissions from stocks, the effluents and sludges that turn rivers into open sewers, and municipal dumps in seventeen chapters. The final chapter lists terms and concepts used in waste technology, organizations concerned with waste management, and sources of information about recycling waste. (MCW)

  10. Waste management

    International Nuclear Information System (INIS)

    Soule, H.F.

    1975-01-01

    Current planning for the management of radioactive wastes, with some emphasis on plutonium contaminated wastes, includes the provision of re-positories from which the waste can be safely removed to permanent disposal. A number of possibilities for permanent disposal are under investigation with the most favorable, at the present time, apparently disposal in a stable geological formation. However, final choice cannot be made until all studies are completed and a pilot phase demonstrates the adequacy of the chosen method. The radioactive wastes which result from all portions of the fuel cycle could comprise an important source of exposure to the public if permitted to do so. The objectives of the AEC waste management program are to provide methods of treating, handling and storing these wastes so that this exposure will not occur. This paper is intended to describe some of the problems and current progress of waste management programs, with emphasis on plutonium-contaminated wastes. Since the technology in this field is advancing at a rapid pace, the descriptions given can be regarded only as a snapshot at one point in time. (author)

  11. Sawmill "Waste"

    Science.gov (United States)

    Fred C. Simmons; Adna R. Bond

    1955-01-01

    Sawmills have the reputation of being very wasteful in converting logs and bolts into lumber and timbers. Almost everyone has seen the great heaps of sawdust and slabs that collect at sawmills. Frequently the question is asked, "Why doesn't somebody do something about this terrible waste of wood?"

  12. Waste Disposal

    International Nuclear Information System (INIS)

    Neerdael, B.; Marivoet, J.; Put, M.; B-Verstricht, J.; Van Iseghem, P.; Buyens, M.

    1998-01-01

    This contribution describes the main activities of the Waste and Disposal Department of the Belgian Nuclear Research Center SCK-CEN. Achievements in 1997 in three topical areas are reported on: performance assessments, waste forms/packages and near-and far field studies

  13. Nuclear waste

    International Nuclear Information System (INIS)

    1992-05-01

    The Nuclear Waste Policy Act of 1982, as amended in 1987, directed the Secretary of Energy to, among other things, investigate Yucca Mountain, Nevada, as a potential site for permanently disposing of highly radioactive wastes in an underground repository. In April 1991, the authors testified on Yucca Mountain project expenditures before your Subcommittee. Because of the significance of the authors findings regrading DOE's program management and expenditures, you asked the authors to continue reviewing program expenditures in depth. As agreed with your office, the authors reviewed the expenditures of project funds made available to the Department of Energy's (DOE) Lawrence Livermore National Laboratory, which is the lead project contractor for developing a nuclear waste package that wold be used for disposing of nuclear waste at Yucca Mountain. This report discusses the laboratory's use of nuclear waste funds to support independent research projects and to manage Yucca Mountain project activities. It also discusses the laboratory's project contracting practices

  14. Nuclear waste

    International Nuclear Information System (INIS)

    Anon.

    1996-01-01

    The NEA Nuclear Waste Bulletin has been prepared by the Radiation Protection and Waste Management Division of the OECD Nuclear Energy Agency to provide a means of communication amongst the various technical and policy groups within the waste management community. In particular, it is intended to provide timely and concise information on radioactive waste management activities, policies and programmes in Member countries and at the NEA. It is also intended that the Bulletin assists in the communication of recent developments in a variety of areas contributing to the development of acceptable technology for the management and disposal of nuclear waste (e.g., performance assessment, in-situ investigations, repository engineering, scientific data bases, regulatory developments, etc)

  15. Nuclear waste

    International Nuclear Information System (INIS)

    Pligt, J. van der

    1989-01-01

    This chapter present a brief overview of the current situation of siting radioactive wastes. This is followed by an overview of various psychological approaches attempting to analyse public reactions to nuclear facilities. It will be argued that public reactions to nuclear waste factilities must be seen in the context of more general attitudes toward nuclear energy. The latter are not only based upon perceptions of the health and environmental risks but are built on values, and sets of attributes which need not be similar to the representations o the experts and policy-makers. The issue of siting nuclear waste facilities is also embedded in a wider moral and political domain. This is illustrated by the importance of equity issues in siting radioactive wastes. In the last section, the implications of the present line of argument for risk communication and public participation in decisions about siting radioactive wastes will be briefly discussed. (author). 49 refs

  16. Waste disposal

    International Nuclear Information System (INIS)

    2005-01-01

    Radioactive waste, as a unavoidable remnant from the use of radioactive substances and nuclear technology. It is potentially hazardous to health and must therefore be managed to protect humans and the environment. The main bulk of radioactive waste must be permanently disposed in engineered repositories. Appropriate safety standards for repository design and construction are required along with the development and implementation of appropriate technologies for the design, construction, operation and closure of the waste disposal systems. As backend of the fuel cycle, resolving the issue of waste disposal is often considered as a prerequisite to the (further) development of nuclear energy programmes. Waste disposal is therefore an essential part of the waste management strategy that contributes largely to build confidence and helps decision-making when appropriately managed. The International Atomic Energy Agency provides assistance to Member States to enable safe and secure disposal of RW related to the development of national RWM strategies, including planning and long-term project management, the organisation of international peer-reviews for research and demonstration programmes, the improvement of the long-term safety of existing Near Surface Disposal facilities including capacity extension, the selection of potential candidate sites for different waste types and disposal options, the characterisation of potential host formations for waste facilities and the conduct of preliminary safety assessment, the establishment and transfer of suitable technologies for the management of RW, the development of technological solutions for some specific waste, the building of confidence through training courses, scientific visits and fellowships, the provision of training, expertise, software or hardware, and laboratory equipment, and the assessment of waste management costs and the provision of advice on cost minimisation aspects

  17. Disposal Of Waste Matter

    International Nuclear Information System (INIS)

    Kim, Jeong Hyeon; Lee, Seung Mu

    1989-02-01

    This book deals with disposal of waste matter management of soiled waste matter in city with introduction, definition of waste matter, meaning of management of waste matter, management system of waste matter, current condition in the country, collect and transportation of waste matter disposal liquid waste matter, industrial waste matter like plastic, waste gas sludge, pulp and sulfuric acid, recycling technology of waste matter such as recycling system of Black clawson, Monroe and Rome.

  18. Waste management

    International Nuclear Information System (INIS)

    Dworschak, H.; Mannone, F.; Rocco, P.

    1995-01-01

    The presence of tritium in tritium-burning devices to be built for large scale research on thermonuclear fusion poses many problems especially in terms of occupational and environmental safety. One of these problems derives from the production of tritiated wastes in gaseous, liquid and solid forms. All these wastes need to be adequately processed and conditioned to minimize tritium releases to an acceptably low occupational and environmental level and consequently to protect workers and the public against the risks of unacceptable doses from exposure to tritium. Since all experimental thermonuclear fusion devices of the Tokomak type to be built and operated in the near future as well as all experimental activities undertaken in tritium laboratories like ETHEL will generate tritiated wastes, current strategies and practices to be applied for the routine management of these wastes need to be defined. Adequate background information is provided through an exhaustive literature survey. In this frame alternative tritiated waste management options so far investigated or currently applied to this end in Europe, USA and Canada have been assessed. The relevance of tritium in waste containing gamma-emitters, originated by the neutron activation of structural materials is assessed in relation to potential final disposal options. Particular importance has been attached to the tritium retention efficiency achievable by the various waste immobilization options. 19 refs., 2 figs., 1 tab

  19. Waste segregation

    International Nuclear Information System (INIS)

    Clark, D.E.; Colombo, P.

    1982-01-01

    A scoping study has been undertaken to determine the state-of-the-art of waste segregation technology as applied to the management of low-level waste (LLW). Present-day waste segregation practices were surveyed through a review of the recent literature and by means of personal interviews with personnel at selected facilities. Among the nuclear establishments surveyed were Department of Energy (DOE) laboratories and plants, nuclear fuel cycle plants, public and private laboratories, institutions, industrial plants, and DOE and commercially operated shallow land burial sites. These survey data were used to analyze the relationship between waste segregation practices and waste treatment/disposal processes, to assess the developmental needs for improved segregation technology, and to evaluate the costs and benefits associated with the implementation of waste segregation controls. This task was planned for completion in FY 1981. It should be noted that LLW management practices are now undergoing rapid change such that the technology and requirements for waste segregation in the near future may differ significantly from those of the present day. 8 figures

  20. Nuclear wastes

    International Nuclear Information System (INIS)

    2002-01-01

    This scientific document presents an introduction to the nuclear wastes problems, the separation process and the transmutation, the political and technical aspects of the storage, the radioprotection standards and the biological effects. (A.L.B.)

  1. Waste Facilities

    Data.gov (United States)

    Vermont Center for Geographic Information — This dataset was developed from the Vermont DEC's list of certified solid waste facilities. It includes facility name, contact information, and the materials...

  2. Nuclear waste

    International Nuclear Information System (INIS)

    1989-01-01

    This paper reviews the Department of Energy's management of underground single-shell waste storage tanks at its Hanford, Washington, site. The tanks contain highly radioactive and nonradioactive hazardous liquid and solid wastes from nuclear materials production. Hundreds of thousands of gallons of these wastes have leaked, contaminating the soil, and a small amount of leaked waste has reached the groundwater. DOE does not collect sufficient data to adequately trace the migration of the leaks through the soil, and studies predicting the eventual environmental impact of tank leaks do not provide convincing support for DOE's conclusion that the impact will be low or nonexistent. DOE can do more to minimize the environmental risks associated with leaks. To reduce the environmental impact of past leaks, DOE may be able to install better ground covering over the tanks to reduce the volume of precipitation that drains through the soil and carries contaminants toward groundwater

  3. Radioactive wastes

    International Nuclear Information System (INIS)

    Dupuis, M.C.

    2007-01-01

    Managing radioactive wastes used to be a peripheral activity for the French atomic energy commission (Cea). Over the past 40 years, it has become a full-fledged phase in the fuel cycle of producing electricity from the atom. In 2005, the national radioactive waste management agency (ANDRA) presented to the government a comprehensive overview of the results drawn from 15 years of research. This landmark report has received recognition beyond France's borders. By broadening this agency's powers, an act of 28 June 2006 acknowledges the progress made and the quality of the results. It also sets an objective for the coming years: work out solutions for managing all forms of radioactive wastes. The possibility of recovering wastes packages from the disposal site must be assured as it was asked by the government in 1998. The next step will be the official demand for the creation of a geological disposal site in 2016

  4. Radioactive waste management

    International Nuclear Information System (INIS)

    2013-01-01

    This eighth chapter presents the radioactive wastes and waste disposal; classification of radioactive wastes; basis requests of the radioactive waste management; conditions for a radioactive waste disposal; registers and inventories; transport of radioactive wastes from a facility to another and the radioactive waste management plan

  5. Tribal Waste Management Program

    Science.gov (United States)

    The EPA’s Tribal Waste Management Program encourages environmentally sound waste management practices that promote resource conservation through recycling, recovery, reduction, clean up, and elimination of waste.

  6. Gelidium elegans, an edible red seaweed, and hesperidin inhibit lipid accumulation and production of reactive oxygen species and reactive nitrogen species in 3T3-L1 and RAW264.7 cells.

    Science.gov (United States)

    Jeon, Hui-Jeon; Seo, Min-Jung; Choi, Hyeon-Son; Lee, Ok-Hwan; Lee, Boo-Yong

    2014-11-01

    Gelidium elegans is an edible red alga native to the intertidal area of northeastern Asia. We investigated the effect of G. elegans extract and its main flavonoids, rutin and hesperidin, on lipid accumulation and the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in 3T3-L1 and RAW264.7 cells. Our data show that G. elegans extract decreased lipid accumulation and ROS/RNS production in a dose-dependent manner. The extract also inhibited the mRNA expression of adipogenic transcription factors, such as peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha, while enhancing the protein expression of the antioxidant enzymes superoxide dismutases 1 and 2, glutathione peroxidase, and glutathione reductase compared with controls. In addition, lipopolysaccharide-induced nitric oxide production was significantly reduced in G. elegans extract-treated RAW264.7 cells. In analysis of the effects of G. elegans flavonoids on lipid accumulation and ROS/RNS production, only hesperidin showed an inhibitory effect on lipid accumulation and ROS production; rutin did not affect adipogenesis and ROS status. The antiadipogenic effect of hesperidin was evidenced by the downregulation of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, and fatty acid binding protein 4 gene expression. Collectively, our data suggest that G. elegans is a potential food source containing antiobesity and antioxidant constituents. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Fluoxetine up-regulates expression of cellular FLICE-inhibitory protein and inhibits LPS-induced apoptosis in hippocampus-derived neural stem cell

    International Nuclear Information System (INIS)

    Chiou, S.-H.; Chen, S.-J.; Peng, C-H.; Chang, Y.-L.; Ku, H.-H.; Hsu, W.-M.; Ho, Larry L.-T.; Lee, C.-H.

    2006-01-01

    Fluoxetine is a widely used antidepressant compound which inhibits the reuptake of serotonin in the central nervous system. Recent studies have shown that fluoxetine can promote neurogenesis and improve the survival rate of neurons. However, whether fluoxetine modulates the proliferation or neuroprotection effects of neural stem cells (NSCs) needs to be elucidated. In this study, we demonstrated that 20 μM fluoxetine can increase the cell proliferation of NSCs derived from the hippocampus of adult rats by MTT test. The up-regulated expression of Bcl-2, Bcl-xL and the cellular FLICE-inhibitory protein (c-FLIP) in fluoxetine-treated NSCs was detected by real-time RT-PCR. Our results further showed that fluoxetine protects the lipopolysaccharide-induced apoptosis in NSCs, in part, by activating the expression of c-FLIP. Moreover, c-FLIP induction by fluoxetine requires the activation of the c-FLIP promoter region spanning nucleotides -414 to -133, including CREB and SP1 sites. This effect appeared to involve the phosphatidylinositol-3-kinase-dependent pathway. Furthermore, fluoxetine treatment significantly inhibited the induction of proinflammatory factor IL-1β, IL-6, and TNF-α in the culture medium of LPS-treated NSCs (p < 0.01). The results of high performance liquid chromatography coupled to electrochemical detection further confirmed that fluoxentine increased the functional production of serotonin in NSCs. Together, these data demonstrate the specific activation of c-FLIP by fluoxetine and indicate the novel role of fluoxetine for neuroprotection in the treatment of depression

  8. Administration of PDE4 Inhibitors Suppressed the Pannus-Like Inflammation by Inhibition of Cytokine Production by Macrophages and Synovial Fibroblast Proliferation

    Directory of Open Access Journals (Sweden)

    Katsuya Kobayashi

    2007-01-01

    Full Text Available A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA. Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4 inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1β, TNF-α, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-α and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

  9. Administration of PDE4 inhibitors suppressed the pannus-like inflammation by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

    Science.gov (United States)

    Kobayashi, Katsuya; Suda, Toshio; Manabe, Haruhiko; Miki, Ichiro

    2007-01-01

    A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA). Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4) inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA) were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1beta, TNF-alpha, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-alpha and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

  10. Nuclear waste

    International Nuclear Information System (INIS)

    1988-01-01

    As required by the Nuclear Waste Policy Act of 1982, the Department of Energy is to annually determine whether the waste disposal fee will produce sufficient revenues to offset the total estimated costs of the waste disposal program. In its June 1987 assessment, DOE recommended that the fee remain unchanged even though its analysis showed that at an inflation rate of 4 percent the current fee would result in end-of-program deficits ranging from $21 billion to $76 billion in 2085. The 1988 assessment calls for reduced total costs because of program changes. Thus, DOE may be able to begin using a realistic inflation rate in determining fee adequacy in 1988 without proposing a major fee increase

  11. Waste processing air cleaning

    International Nuclear Information System (INIS)

    Kriskovich, J.R.

    1998-01-01

    Waste processing and preparing waste to support waste processing relies heavily on ventilation. Ventilation is used at the Hanford Site on the waste storage tanks to provide confinement, cooling, and removal of flammable gases

  12. Radioactive Waste Management Strategy

    International Nuclear Information System (INIS)

    2002-01-01

    This strategy defines methods and means how collect, transport and bury radioactive waste safely. It includes low level radiation waste and high level radiation waste. In the strategy are foreseen main principles and ways of storage radioactive waste

  13. Disposal of radioactive wastes

    International Nuclear Information System (INIS)

    Dlouhy, Z.

    1982-01-01

    This book provides information on the origin, characteristics and methods of processing of radioactive wastes, as well as the philosophy and practice of their storage and disposal. Chapters are devoted to the following topics: radioactive wastes, characteristics of radioactive wastes, processing liquid and solid radioactive wastes, processing wastes from spent fuel reprocessing, processing gaseous radioactive wastes, fixation of radioactive concentrates, solidification of high-level radioactive wastes, use of radioactive wastes as raw material, radioactive waste disposal, transport of radioactive wastes and economic problems of radioactive wastes disposal. (C.F.)

  14. Human waste

    NARCIS (Netherlands)

    Amin, Md Nurul; Kroeze, Carolien; Strokal, Maryna

    2017-01-01

    Many people practice open defecation in south Asia. As a result, lot of human waste containing nutrients such as nitrogen (N) and phosphorus (P) enter rivers. Rivers transport these nutrients to coastal waters, resulting in marine pollution. This source of nutrient pollution is, however, ignored in

  15. Waste disposal

    CERN Multimedia

    2006-01-01

    We should like to remind you that you can have all commonplace, conventional waste (combustible, inert, wood, etc.) disposed of by the TS-FM Group. Requests for the removal of such waste should be made by contacting FM Support on tel. 77777 or by e-mail (Fm.Support@cern.ch). For requests to be acted upon, the following information must be communicated to FM Support: budget code to be debited for the provision and removal of the skip / container. type of skip required (1m3, 4 m3, 7 m3, 15 m3, 20 m3, 30 m3). nature of the waste to be disposed of (bulky objects, cardboard boxes, etc.). building concerned. details of requestor (name, phone number, department, group, etc.). We should also like to inform you that the TS-FM Group can arrange for waste to be removed from work-sites for firms under contract to CERN, provided that the prior authorisation of the CERN Staff Member in charge of the contract is obtained and the relevant disposal/handling charges are paid. You are reminded that the selective sorting o...

  16. Waste disposal

    CERN Multimedia

    2006-01-01

    We should like to remind you that you can have all commonplace, conventional waste (combustible, inert, wood, etc.) disposed of by the TS-FM Group. Requests for the removal of such waste should be made by contacting FM Support on tel. 77777 or by e-mail (Fm.Support@cern.ch). For requests to be acted upon, the following information must be communicated to FM Support: budget code to be debited for the provision and removal of the skip / container; type of skip required (1m3, 4 m3, 7 m3, 15 m3, 20 m3, 30 m3); nature of the waste to be disposed of (bulky objects, cardboard boxes, etc.); building concerned; details of requestor (name, phone number, department, group, etc.). We should also like to inform you that the TS-FM Group can arrange for waste to be removed from work-sites for firms under contract to CERN, provided that the prior authorisation of the CERN Staff Member in charge of the contract is obtained and the relevant disposal/handling charges are paid. You are reminded that the selective sorting...

  17. INHIBITION IN SPEAKING PERFORMANCE

    OpenAIRE

    Humaera, Isna

    2015-01-01

    The most common problem encountered by the learner in the languageacquisition process is learner inhibition. Inhibition refers to a temperamentaltendency to display wariness, fearfulness, or restrain in response tounfamiliar people, objects, and situations. There are some factors that causeinhibition, such as lack of motivation, shyness, self-confidence, self-esteem,and language ego. There are also levels of inhibition, it refers to kinds ofinhibition and caused of inhibition itself. Teacher ...

  18. Cordycepin alleviates lipopolysaccharide-induced acute lung injury via Nrf2/HO-1 pathway.

    Science.gov (United States)

    Qing, Rui; Huang, Zezhi; Tang, Yufei; Xiang, Qingke; Yang, Fan

    2018-04-24

    The present study is to investigate the protective effect of cordycepin on inflammatory reactions in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS), as well as the underlying mechanism. Wistar rat model of ALI was induced by intravenous injection of LPS (30 mg/kg body weight). One hour later, intravenous injection of cordycepin (1, 10 or 30 mg/kg body weight) was administered. The wet-to-dry weight ratio of lung tissues and myeloperoxidase activity in the lung tissues were measured. The contents of nitrite and nitrate were measured by reduction method, while chemiluminescence was used to determine the content of superoxide. Quantitative real-time polymerase chain reaction and Western blotting were used to determine the expression of mRNA and protein, respectively. Colorimetry was performed to determine the enzymatic activity of heme oxygenase-1 (HO-1). Nuclear translocation of Nrf2 was identified by Western blotting. The plasma contents of cytokines were measured by enzyme-linked immunosorbent assay. Cordycepin enhanced the expression and enzymatic activity of HO-1 in ALI rats, and activated Nrf2 by inducing the translocation of Nrf2 from cytoplasm to nucleus. In addition, cordycepin regulated the secretion of TNF-α, IL-6 and IL-10 via HO-1, and suppressed inflammation in lung tissues of ALI rats by inducing the expression of HO-1. HO-1 played important roles in the down-regulation of superoxide levels in lung tissues by cordycepin, and HO-1 expression induced by cordycepin affected nitrite and nitrate concentrations in plasma and iNOS protein expression in lung tissues. Cordycepin showed protective effect on injuries in lung tissues. The present study demonstrates that cordycepin alleviates inflammation induced by LPS via the activation of Nrf2 and up-regulation of HO-1 expression. Copyright © 2018. Published by Elsevier B.V.

  19. Spred-2 deficiency exacerbates lipopolysaccharide-induced acute lung inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Yang Xu

    Full Text Available BACKGROUND: Acute respiratory distress syndrome (ARDS is a severe and life-threatening acute lung injury (ALI that is caused by noxious stimuli and pathogens. ALI is characterized by marked acute inflammation with elevated alveolar cytokine levels. Mitogen-activated protein kinase (MAPK pathways are involved in cytokine production, but the mechanisms that regulate these pathways remain poorly characterized. Here, we focused on the role of Sprouty-related EVH1-domain-containing protein (Spred-2, a negative regulator of the Ras-Raf-extracellular signal-regulated kinase (ERK-MAPK pathway, in lipopolysaccharide (LPS-induced acute lung inflammation. METHODS: Wild-type (WT mice and Spred-2(-/- mice were exposed to intratracheal LPS (50 µg in 50 µL PBS to induce pulmonary inflammation. After LPS-injection, the lungs were harvested to assess leukocyte infiltration, cytokine and chemokine production, ERK-MAPK activation and immunopathology. For ex vivo experiments, alveolar macrophages were harvested from untreated WT and Spred-2(-/- mice and stimulated with LPS. In in vitro experiments, specific knock down of Spred-2 by siRNA or overexpression of Spred-2 by transfection with a plasmid encoding the Spred-2 sense sequence was introduced into murine RAW264.7 macrophage cells or MLE-12 lung epithelial cells. RESULTS: LPS-induced acute lung inflammation was significantly exacerbated in Spred-2(-/- mice compared with WT mice, as indicated by the numbers of infiltrating leukocytes, levels of alveolar TNF-α, CXCL2 and CCL2 in a later phase, and lung pathology. U0126, a selective MEK/ERK inhibitor, reduced the augmented LPS-induced inflammation in Spred-2(-/- mice. Specific knock down of Spred-2 augmented LPS-induced cytokine and chemokine responses in RAW264.7 cells and MLE-12 cells, whereas Spred-2 overexpression decreased this response in RAW264.7 cells. CONCLUSIONS: The ERK-MAPK pathway is involved in LPS-induced acute lung inflammation. Spred-2 controls the development of LPS-induced lung inflammation by negatively regulating the ERK-MAPK pathway. Thus, Spred-2 may represent a therapeutic target for the treatment of ALI.

  20. Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats

    DEFF Research Database (Denmark)

    Schmal, H; Shanley, T P; Jones, M L

    1996-01-01

    Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that possesses chemotactic activity for neutrophils. Rat MIP-2 was cloned and expressed as a 7.9-kDa peptide that exhibited dose-dependent neutrophil chemotactic activity at concentrations from 10 to 250 nM. Rabbit polyclonal Ab to th...... instillation of LPS was found to be MIP-2-dependent. These data indicate that MIP-2 plays a significant role in LPS-induced inflammatory response in rat lungs and is required for the full recruitment of neutrophils....

  1. Antioxidant properties of lutein contribute to the protection against lipopolysaccharide-induced uveitis in mice

    Directory of Open Access Journals (Sweden)

    Yao Xin-Sheng

    2011-10-01

    Full Text Available Abstract Background Lutein is an important eye-protective nutrient. This study investigates the protective effects and mechanisms of lutein on lipopolysaccharides (LPS-induced uveitis in mice. Methods Lutein, suspended in drinking water at a final concentration of 12.5 and 25 mg/mL, was administered to mice at 0.1 mL/10 g body weight for five consecutive days. Control and model group received drinking water only. Uveitis was induced by injecting LPS (100 mg per mouse into the footpad in the model and lutein groups on day 5 after the last drug administration. Eyes of the mice were collected 24 hours after the LPS injection for the detection of indicators using commercial kits and reverse transcription-polymerase chain reaction. Results LPS-induced uveitis was confirmed by significant pathological damage and increased the nitric oxide level in eye tissue of BALB/C mice 24 hours after the footpad injection. The elevated nitric oxide level was significantly reduced by oral administration of lutein (125 and 500 mg/kg/d for five days before LPS injection. Moreover, lutein decreased the malondialdehyde content, increased the oxygen radical absorbance capacity level, glutathione, the vitamin C contents and total superoxide dismutase (SOD and glutathione peroxidase (GPx activities. Lutein further increased expressions of copper-zinc SOD, manganese SOD and GPx mRNA. Conclusion The antioxidant properties of lutein contribute to the protection against LPS-induced uveitis, partially through the intervention of inflammation process.

  2. Static Magnetic Field Attenuates Lipopolysaccharide-Induced Inflammation in Pulp Cells by Affecting Cell Membrane Stability

    Directory of Open Access Journals (Sweden)

    Sung-Chih Hsieh

    2015-01-01

    Full Text Available One of the causes of dental pulpitis is lipopolysaccharide- (LPS- induced inflammatory response. Following pulp tissue inflammation, odontoblasts, dental pulp cells (DPCs, and dental pulp stem cells (DPSCs will activate and repair damaged tissue to maintain homeostasis. However, when LPS infection is too serious, dental repair is impossible and disease may progress to irreversible pulpitis. Therefore, the aim of this study was to examine whether static magnetic field (SMF can attenuate inflammatory response of dental pulp cells challenged with LPS. In methodology, dental pulp cells were isolated from extracted teeth. The population of DPSCs in the cultured DPCs was identified by phenotypes and multilineage differentiation. The effects of 0.4 T SMF on DPCs were observed through MTT assay and fluorescent anisotropy assay. Our results showed that the SMF exposure had no effect on surface markers or multilineage differentiation capability. However, SMF exposure increases cell viability by 15%. In addition, SMF increased cell membrane rigidity which is directly related to higher fluorescent anisotropy. In the LPS-challenged condition, DPCs treated with SMF demonstrated a higher tolerance to LPS-induced inflammatory response when compared to untreated controls. According to these results, we suggest that 0.4 T SMF attenuates LPS-induced inflammatory response to DPCs by changing cell membrane stability.

  3. Ficolins do not alter host immune responses to lipopolysaccharide-induced inflammation in vivo

    DEFF Research Database (Denmark)

    Genster, Ninette; Østrup, Olga; Schjalm, Camilla

    2017-01-01

    . Yet, the contribution of ficolins to inflammatory disease processes remains elusive. To address this, we investigated ficolin deficient mice during a lipopolysaccharide (LPS)-induced model of systemic inflammation. Although murine serum ficolin was shown to bind LPS in vitro, there was no difference...... an unaltered spleen transcriptome profile in ficolin deficient mice compared to wildtype mice. Collectively, results from this study demonstrate that ficolins are not involved in host response to LPS-induced systemic inflammation.......Ficolins are a family of pattern recognition molecules that are capable of activating the lectin pathway of complement. A limited number of reports have demonstrated a protective role of ficolins in animal models of infection. In addition, an immune modulatory role of ficolins has been suggested...

  4. Resveratrol protects from lipopolysaccharide-induced inflammation in the uterus and prevents experimental preterm birth.

    Science.gov (United States)

    Bariani, María Victoria; Correa, Fernando; Leishman, Emma; Domínguez Rubio, Ana Paula; Arias, Andreína; Stern, Aníbal; Bradshaw, Heather B; Franchi, Ana María

    2017-08-01

    Is resveratrol able to prevent the lipopolysaccharide (LPS)-induced preterm labor in 15-day pregnant BALB/c mice? Resveratrol prevented the LPS-induced onset of preterm labor in 64% of the cases and showed anti-inflammatory and tocolytic effects by downregulating COX-2 and iNOS expression and NOS activity, and by changing the uterine prostaglandin and endocannabinoid profiling. Genital tract infections by Gram-negative bacteria are a common complication in human pregnancy and have been shown to increase risk of preterm delivery. Bacterial LPS elicits a strong maternal inflammatory response that results in preterm delivery and fetal death in a murine model endotoxin-induced preterm labor. An in vivo animal study was conducted. On Day 15 of pregnancy, mice received at 8:00 h a dose of vehicle (40% ethanol in saline solution) or resveratrol (3 mg/kg in vehicle) via oral gavage followed by two doses of LPS or vehicle administered intraperitoneally (i.p.), the first one at 10:00 h (0.17 mg/kg in 0.1 ml of sterile saline solution) and the second at 13:00 h (0.5 mg/kg in 0.1 ml of sterile saline solution). The mice were closely observed for any signs of morbidity (piloerection, decreased movement, and diarrhea), vaginal bleeding or preterm delivery. The beginning of preterm delivery was defined by early delivery of the first pup. Normal term labor occurs on Day 19 of gestation. Time of labor, pregnancy outcome and morphological features were evaluated after LPS and/or resveratrol administration. Uterine stripes were collected 5 h after the last LPS injection and prostaglandin and endocannabinoid profiling was analyzed by mass spectrometry. Nitric oxide synthase (NOS) activity was measured by radioconversion assay. Cyclooxygenase-2 (Cox-2) and 15-hydroxyprostaglandin dehydrogenase (15-Pgdh) mRNA levels were analyzed by RT-PCR whilst the protein expression of inducible nitric oxide synthase (iNOS), COX-1 and COX-2 were studied by western blot. In vivo treatment of 15-day pregnant BALB/c mice with resveratrol prevented the LPS-induced preterm birth in 64% of the cases, whereas only 15% of mice with LPS alone escaped preterm birth. Treatment with resveratrol resulted in a reduced NOS activity (P resveratrol reduced the expression of LPS-induced pro-inflammatory agents such as iNOS (P resveratrol administration resulted in changes in the uterine endocannabinoid profiling altered by LPS. N/A. Since our experimental design involves the use of mice, the extrapolation of the results presented here to humans is limited. Our findings provide evidence for the tocolytic effects of resveratrol. Dr Ana María Franchi was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2013/0097) and by Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 2012/0061). Dr Heather B. Bradshaw was funded by NIH (DA006668). The authors have no competing interests. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  5. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS

    Directory of Open Access Journals (Sweden)

    REYHANEH SEPEHR

    2013-07-01

    Full Text Available Reactive oxygen species (ROS have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI in adults and bronchopulmonary dysplasia (BPD in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD, referred to as NADH redox ratio (NADH RR has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2 pups, hyperoxic (90% O2 pups, pups treated with LPS (normoxic + LPS, and pups treated with LPS and hyperoxia (hyperoxic + LPS. Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~ 31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

  6. Early Effects of Lipopolysaccharide-Induced Inflammation on Foetal Brain Development in Rat

    Directory of Open Access Journals (Sweden)

    Cristina A Ghiani

    2011-10-01

    Full Text Available Studies in humans and animal models link maternal infection and imbalanced levels of inflammatory mediators in the foetal brain to the aetiology of neuropsychiatric disorders. In a number of animal models, it was shown that exposure to viral or bacterial agents during a period that corresponds to the second trimester in human gestation triggers brain and behavioural abnormalities in the offspring. However, little is known about the early cellular and molecular events elicited by inflammation in the foetal brain shortly after maternal infection has occurred. In this study, maternal infection was mimicked by two consecutive intraperitoneal injections of 200 μg of LPS (lipopolysaccharide/kg to timed-pregnant rats at GD15 (gestational day 15 and GD16. Increased thickness of the CP (cortical plate and hippocampus together with abnormal distribution of immature neuronal markers and decreased expression of markers for neural progenitors were observed in the LPS-exposed foetal forebrains at GD18. Such effects were accompanied by decreased levels of reelin and the radial glial marker GLAST (glial glutamate transporter, and elevated levels of pro-inflammatory cytokines in maternal serum and foetal forebrains. Foetal inflammation elicited by maternal injections of LPS has discrete detrimental effects on brain development. The early biochemical and morphological changes described in this work begin to explain the sequelae of early events that underlie the neurobehavioural deficits reported in humans and animals exposed to prenatal insults.

  7. Modulation of lipopolysaccharide-induced chorioamnionitis in fetal sheep by maternal betamethasone.

    Science.gov (United States)

    Wolfe, Katherine B; Snyder, Candice C; Gisslen, Tate; Kemp, Matthew W; Newnham, John P; Kramer, Boris W; Jobe, Alan H; Kallapur, Suhas

    2013-12-01

    We tested the hypothesis that the order of exposure to maternal betamethasone and intra-amniotic (IA) lipopolysaccharide (LPS) will differentially modulate inflammation in the chorioamnion. Time-mated Merino ewes with singleton fetuses received saline alone, IA LPS alone, maternal betamethasone before LPS, or betamethasone after LPS. We assessed inflammatory markers in the chorioamnion and the amniotic fluid. Inflammatory cell infiltration, expression of myeloperoxidase, serum amyloid A3 (acute phase reactant) in the chorioamnion, and levels of interleukin (IL)-8 in the amniotic fluid increased 7 days after LPS exposure. Betamethasone prior to LPS decreased infiltration of the inflammatory cells, CD3+ T cells, and decreased the levels of IL-1β and IL-8 in the amniotic fluid. Betamethasone 7 days prior to LPS exposure suppressed LPS-induced inflammation. The markers of inflammation largely had returned to the baseline 14 days after LPS exposure.

  8. Modulation of lipopolysaccharide-induced chorioamnionitis by Ureaplasma parvum in sheep.

    Science.gov (United States)

    Snyder, Candice C; Wolfe, Katherine B; Gisslen, Tate; Knox, Christine L; Kemp, Matthew W; Kramer, Boris W; Newnham, John P; Jobe, Alan H; Kallapur, Suhas G

    2013-05-01

    Ureaplasma colonization in the setting of polymicrobial flora is common in women with chorioamnionitis, and is a risk factor for preterm delivery and neonatal morbidity. We hypothesized that Ureaplasma colonization of amniotic fluid would modulate chorioamnionitis induced by Escherichia coli lipopolysaccharide (LPS). Sheep received intraamniotic (IA) injections of media (control) or live Ureaplasma either 7 or 70 days before delivery. Another group received IA LPS 2 days before delivery. To test for interactions, U parvum-exposed animals were challenged with IA LPS, and delivered 2 days later. All animals were delivered preterm at 125 ± 1 day of gestation. Both IA Ureaplasma and LPS induced leukocyte infiltration of chorioamnion. LPS greatly increased the expression of proinflammatory cytokines and myeloperoxidase in leukocytes, while Ureaplasma alone caused modest responses. Interestingly, 7-day but not 70-day Ureaplasma exposure significantly down-regulated LPS-induced proinflammatory cytokines and myeloperoxidase expression in the chorioamnion. Acute (7-day) U parvum exposure can suppress LPS-induced chorioamnionitis. Copyright © 2013 Mosby, Inc. All rights reserved.

  9. Equine colostral carbohydrates reduce lipopolysaccharide-induced inflammatory responses in equine peripheral blood mononuclear cells.

    Science.gov (United States)

    Vendrig, J C; Coffeng, L E; Fink-Gremmels, J

    2012-12-01

    Increasing evidence suggests that reactions to lipopolysaccharide (LPS), particularly in the gut, can be partly or completely mitigated by colostrum- and milk-derived oligosaccharides. Confirmation of this hypothesis could lead to the development of new therapeutic concepts. To demonstrate the influence of equine colostral carbohydrates on the inflammatory response in an in vitro model with equine peripheral blood mononuclear cells (PBMCs). Carbohydrates were extracted from mare colostrum, and then evaluated for their influence on LPS-induced inflammatory responses in PBMCs isolated from the same mares, mRNA expression of tumour necrosis factor-alpha, interleukin-6 and interleukin-10 was measured as well as the protein levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10). Equine colostral carbohydrates significantly reduced LPS-induced TNF-alpha protein at both times measured and significantly reduced LPS-induced TNF-alpha, IL-6 and IL-10 mRNA expression by PBMCs. Moreover, cell viability significantly increased in the presence of high concentrations of colostral carbohydrates. Carbohydrates derived from equine colostrum reduce LPS-induced inflammatory responses of equine PBMCs. Colostrum and milk-derived carbohydrates are promising candidates for new concepts in preventive and regenerative medicine.

  10. LIPOPOLYSACCHARIDE INDUCES THE PRODUCTION OF DIAGNOSTIC MONOCLONAL ANTIBODY BY HYBRIDOMA CELLS AGAINST CONGENITAL ADRENAL HYPERPLASIA

    Directory of Open Access Journals (Sweden)

    GEK KEE CHUA

    2017-11-01

    Full Text Available The purpose of this research is to screen and identify the potential inducers in maximizing the production of monoclonal antibody by hybridoma 192 cell line for Congenital Adrenal Hyperplasia diagnostic. There are nine inducers used in this research, namely lysozyme, aldolase, sodium butyrate, sodium phosphate, potassium phosphate, dimethyl sulfoxide, lipopolysaccharide, essential amino acids, and nonessential amino acids. Hybridoma 192 cell was cultured in 5% CO2 incubator at 37°C and ˃80% humidity in the medium with different concentrations of inducer agents. The inducers were added at the beginning of the culture and the samples were taken after 72 h of culture. The performance of these inducer agents was assessed based on the maximum monoclonal antibody titer achieved using Enzyme-linked Immunosorbent Assay. Lipopolysaccharide was found to increase the maximum monoclonal antibody titer when supplemented at 8 to 12 µg/mL. After optimization using one-factor central composite design at this range, the optimum point was determined to be 8 µg/mL. Verification experiments shows that lipopolysaccharide enhanced the average specific monoclonal antibody production rate by 56% relative to control. In conclusion, lipopolysaccharide at 8 µg/mL is able to increase the monoclonal antibody specific production of hybridoma 192 cell line.

  11. Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation.

    Directory of Open Access Journals (Sweden)

    Takeshi Tohyama

    Full Text Available Lipopolysaccharide (LPS induces acute inflammation, activates sympathetic nerve activity (SNA and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP, examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis.Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg. We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection.In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.. In contrast, AP increased initially (until 75 min, then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP.LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and suppressed peripheral arc determines SNA and hemodynamics in LPS-induced acute inflammation.

  12. Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation.

    Science.gov (United States)

    Tohyama, Takeshi; Saku, Keita; Kawada, Toru; Kishi, Takuya; Yoshida, Keimei; Nishikawa, Takuya; Mannoji, Hiroshi; Kamada, Kazuhiro; Sunagawa, Kenji; Tsutsui, Hiroyuki

    2018-01-01

    Lipopolysaccharide (LPS) induces acute inflammation, activates sympathetic nerve activity (SNA) and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP), examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis. Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg). We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP) by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection. In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.). In contrast, AP increased initially (until 75 min), then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship) upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship) downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP. LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and suppressed peripheral arc determines SNA and hemodynamics in LPS-induced acute inflammation.

  13. Lipopolysaccharide-induced Pulpitis Up-regulates TRPV1 in Trigeminal Ganglia

    Science.gov (United States)

    Chung, M.-K.; Lee, J.; Duraes, G.; Ro, J.Y.

    2011-01-01

    Tooth pain often accompanies pulpitis. Accumulation of lipopolysaccharides (LPS), a product of Gram-negative bacteria, is associated with painful clinical symptoms. However, the mechanisms underlying LPS-induced tooth pain are not clearly understood. TRPV1 is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and hyperalgesia under inflammation or injury. Although TRPV1 is expressed in pulpal afferents, it is not known whether the application of LPS to teeth modulates TRPV1 in trigeminal nociceptors. By assessing the levels of protein and transcript of TRPV1 in mouse trigeminal ganglia, we demonstrate that dentinal application of LPS increases the expression of TRPV1. Our results suggest that the up-regulation of TRPV1 in trigeminal nociceptors following bacterial infection could contribute to hyperalgesia under pulpitis conditions. PMID:21712529

  14. Bacterial lipopolysaccharide induces osteoclast formation in RAW 264.7 macrophage cells

    International Nuclear Information System (INIS)

    Islam, Shamima; Hassan, Ferdaus; Tumurkhuu, Gantsetseg; Dagvadorj, Jargalsaikhan; Koide, Naoki; Naiki, Yoshikazu; Mori, Isamu; Yoshida, Tomoaki; Yokochi, Takashi

    2007-01-01

    Lipopolysaccharide (LPS) is a potent bone resorbing factor. The effect of LPS on osteoclast formation was examined by using murine RAW 264.7 macrophage cells. LPS-induced the formation of multinucleated giant cells (MGC) in RAW 264.7 cells 3 days after the exposure. MGCs were positive for tartrate-resistant acid phosphatase (TRAP) activity. Further, MGC formed resorption pits on calcium-phosphate thin film that is a substrate for osteoclasts. Therefore, LPS was suggested to induce osteoclast formation in RAW 264.7 cells. LPS-induced osteoclast formation was abolished by anti-tumor necrosis factor (TNF)-α antibody, but not antibodies to macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-κB ligand (RANKL). TNF-α might play a critical role in LPS-induced osteoclast formation in RAW 264.7 cells. Inhibitors of NF-κB and stress activated protein kinase (SAPK/JNK) prevented the LPS-induced osteoclast formation. The detailed mechanism of LPS-induced osteoclast formation is discussed

  15. Effect of methanolic extract of Asparagus racemosus Willd. on lipopolysaccharide induced-oxidative stress in rats.

    Science.gov (United States)

    Ahmad, Mohammad Parwez; Hussain, Arshad; Siddiqui, Hefazat Hussain; Wahab, Shadma; Adak, Manoranjan

    2015-03-01

    Lipopolysaccharide (LPS) induced oxidative stress and impairment of normal physiological function generally categorized by increased anxiety and reduced mobility. Therefore, the present study was to find out the effect Methanolic extract of Asparagus racemosus (MEAR ) in lipopolysaccharide (LPS)-induced oxidative stress in rats . LPS-induced oxidative stress in rats was measured by locomotor activity by photoactometer test, anxiety with elevated plus maze test and also studied the oxidative stress markers, nitric oxide and cytokines. The obtained data shows that LPS markedly exhausted (pAsparagus racemosus Willd. is a functionally newer type of cerebroprotective agent.

  16. Chondroitin Sulfate-Rich Extract of Skate Cartilage Attenuates Lipopolysaccharide-Induced Liver Damage in Mice.

    Science.gov (United States)

    Song, Yeong Ok; Kim, Mijeong; Woo, Minji; Baek, Jang-Mi; Kang, Keon-Hee; Kim, Sang-Ho; Roh, Seong-Soo; Park, Chan Hum; Jeong, Kap-Seop; Noh, Jeong-Sook

    2017-06-15

    The protective effects of a chondroitin sulfate-rich extract (CSE) from skate cartilage against lipopolysaccharide (LPS)-induced hepatic damage were investigated, and its mechanism of action was compared with that of chondroitin sulfate (CS) from shark cartilage. ICR mice were orally administrated 200 mg/kg body weight (BW) of CS or 400 mg/kg BW of CSE for 3 consecutive days, followed by a one-time intraperitoneal injection of LPS (20 mg/kg BW). The experimental groups were vehicle treatment without LPS injection (NC group), vehicle treatment with LPS injection (LPS group), CS pretreatment with LPS injection (CS group), and CSE pretreatment with LPS injection (CSE group). Hepatic antioxidant enzyme expression levels in the CS and CSE groups were increased relative to those in the LPS group. In LPS-insulted hepatic tissue, inflammatory factors were augmented relative to those in the NC group, but were significantly suppressed by pretreatment with CS or CSE. Moreover, CS and CSE alleviated the LPS-induced apoptotic factors and mitogen-activated protein kinase (MAPK). In addition, CS and CSE effectively decreased the serum lipid concentrations and downregulated hepatic sterol regulatory element-binding proteins expression. In conclusion, the skate CSE could protect against LPS-induced hepatic dyslipidemia, oxidative stress, inflammation, and apoptosis, probably through the regulation of MAPK signaling.

  17. Effect of anti-podoplanin antibody administration during lipopolysaccharide-induced lung injury in mice.

    Science.gov (United States)

    Lax, Sian; Rayes, Julie; Thickett, David R; Watson, Steve P

    2017-01-01

    Acute respiratory distress syndrome (ARDS) is a devastating pulmonary condition in the critically ill patient. A therapeutic intervention is yet to be found that can prevent progression to ARDS. We recently demonstrated that the interaction between podoplanin expressed on inflammatory alveolar macrophages (iAMs) and its endogenous ligand, platelet C-type lectin-like 2 (CLEC-2), protects against exaggerated lung inflammation during a mouse model of ARDS. In this study, we aim to investigate the therapeutic use of a crosslinking/activating anti-podoplanin antibody (α-PDPN, clone 8.1.1) during lipopolysaccharide (LPS)-induced lung inflammation in mice. Intravenous administration of α-PDPN was performed 6 hours after intratracheal LPS in wildtype, C57Bl/6 mice. Lung function decline was measured by pulse oximetry as well as markers of local inflammation including bronchoalveolar lavage neutrophilia and cytokine/chemokine expression. In parallel, alveolar macrophages were isolated and cultured in vitro from haematopoietic-specific podoplanin-deficient mice (Pdpn fl/fl VAV1cre + ) and floxed-only controls treated with or without LPS in the presence or absence of α-PDPN. Lung function decline as well as alveolar neutrophil recruitment was significantly decreased in mice treated with the crosslinking/activating α-PDPN in vivo. Furthermore, we demonstrate that, in vitro, activation of podoplanin on iAMs regulates their secretion of proinflammatory cytokines and chemokines. These data confirm the importance of the CLEC-2-podoplanin pathway during intratracheal (IT)-LPS and demonstrate the beneficial effect of targeting podoplanin during IT-LPS in mice possibly via modulation of local cytokine/chemokine expression. Moreover, these data suggest that podoplanin-targeted therapies may have a beneficial effect in patients at risk of developing ARDS.

  18. Rabdosia japonica var. glaucocalyx Flavonoids Fraction Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice

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    Chun-jun Chu

    2014-01-01

    Full Text Available Rabdosia japonica var. glaucocalyx (Maxim. Hara, belonging to the Labiatae family, is widely used as an anti-inflammatory and antitumor drug for the treatment of different inflammations and cancers. Aim of the Study. To investigate therapeutic effects and possible mechanism of the flavonoids fraction of Rabdosia japonica var. glaucocalyx (Maxim. Hara (RJFs in acute lung injury (ALI mice induced by lipopolysaccharide (LPS. Materials and Methods. Mice were orally administrated with RJFs (6.4, 12.8, and 25.6 mg/kg per day for 7 days, consecutively, before LPS challenge. Lung specimens and the bronchoalveolar lavage fluid (BALF were isolated for histopathological examinations and biochemical analysis. The level of complement 3 (C3 in serum was quantified by a sandwich ELISA kit. Results. RJFs significantly attenuated LPS-induced ALI via reducing productions of the level of inflammatory mediators (TNF-α, IL-6, and IL-1β, and significantly reduced complement deposition with decreasing the level of C3 in serum, which was exhibited together with the lowered myeloperoxidase (MPO activity and nitric oxide (NO and protein concentration in BALF. Conclusions. RJFs significantly attenuate LPS-induced ALI via reducing productions of proinflammatory mediators, decreasing the level of complement, and reducing radicals.

  19. Pharmacologic studies on ET-26 hydrochloride in a rat model of lipopolysaccharide-induced sepsis.

    Science.gov (United States)

    Wang, Bin; Jiang, Junli; Yang, Jun; Chen, Jun; Zhu, Zhaoqiong; Liu, Jin; Zhang, Wensheng

    2017-11-15

    ET-26 hydrochloride (ET-26 HCl) is a promising sedation-hypnotic compound with stable hemodynamic features that elicits virtually no adrenocortical suppression. However, whether it preserves better pharmacologic characteristics in a rat model of sepsis is not known. This study compared the survival rate, levels of corticosterone and pro-inflammatory cytokines, and histologic injury in the lungs and kidneys of rats suffering from sepsis treated with ET-26 HCl, etomidate, or normal saline (NS). Rats were given lipopolysaccharide (1mg/kg body weight, i.v.) to establish a sepsis model. Thirty minutes after lipopolysaccharide administration, ET-26 HCl, etomidate or NS were given as a bolus injection at equivalent doses. Plasma levels of corticosterone, interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α were measured 1, 2, 4, 6 and 24h after administration. Histologic injury was observed at the time of death or 24h after drug administration. The survival rate for rats in the etomidate, ET-26 HCl and NS groups was 40%, 90% and 90%, respectively. Corticosterone concentrations in the etomidate group were lower than those in the other groups 1h after administration of hypnotic compounds. Concentrations of pro-inflammatory cytokines in the ET-26 HCl group and NS group were not significantly different, but were significantly lower than those in the etomidate group. The injury scores of kidneys and lungs in the etomidate group were higher than those in ET-26 HCl and NS groups. ET-26 HCl showed virtually no suppression of corticosterone synthesis, lower concentrations of pro-inflammatory cytokines, higher survival rate, and less organ injury in rats suffering from sepsis compared with the etomidate group. It may be safer to induce anesthesia using ET-26 HCl, rather than etomidate, in patients suffering from sepsis. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. The effects of fisetin on lipopolysaccharide-induced depressive-like behavior in mice.

    Science.gov (United States)

    Yu, Xuefeng; Jiang, Xi; Zhang, Xiangming; Chen, Ziwei; Xu, Lexing; Chen, Lei; Wang, Guokang; Pan, Jianchun

    2016-10-01

    Major depressive disorder (MDD) involves a series of pathological changes including the inflammation and increased cytokine levels. Fisetin, a natural flavonoid, has anti-inflammatory and antioxidant, and also has been shown in our previous studies to exert anti-depressant-like properties. The present study aimed to investigate the effect of fisetin on lipopolysaccharide (LPS)-induced depressive-like behavior and inflammation in mice. The results suggested that the immobility time in the forced swimming test (FST) and tail suspension test (TST) were increased at 6 h, 12 h and 24 h after LPS injection (0.83 mg/kg). However, only the group of 24 h treatment did not show any effect on locomotion counts. Pretreatment with fisetin at doses of 20, 40 and 80 mg/kg (p.o.) for 7 days reversed LPS-induced alterations of the immobility time in both of these two tests. Further neurochemical assays suggested that pretreatment with fisetin reversed LPS-induced overexpression of pro-inflammatory cytokine (IL-1β, IL-6 and TNF-α) in the hippocampus and the prefrontal cortex (PFC). Moreover, higher dose of fisetin effectively antagonized iNOS mRNA expression and nitrite levels via the modulation of NF-κB in the hippocampus and PFC. Taken together, fisetin may be an effective therapeutic agent for LPS-induced depressive-like behaviors, which is due to its anti-inflammatory property.

  1. Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation.

    Science.gov (United States)

    Xiong, Xi; Ren, Yuqian; Cui, Yun; Li, Rui; Wang, Chunxia; Zhang, Yucai

    2017-12-01

    Cholestasis, as a main manifestation, induces liver injury during sepsis. The farnesoid X receptor (FXR) plays an important role in regulating bile acid homeostasis. Whether FXR activation by its agonist obeticholic acid (OCA) is contributed to improve sepsis-induced liver injury remains unknown. The aim of the present study was to investigate the effect of OCA on lipopolysaccharide (LPS)-induced acute liver injury in mice. 8-week old male C57BL/6J mice were randomly divided into control group, LPS group, oral OCA group and LPS plus oral OCA (LPS + OCA) group. The serum and livers were collected for further analysis. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and total bilirubin (TBIL) were measured at indicated time after LPS administration. Liver sections were stained with hematoxylin & eosin (H&E). Orally OCA pretreatment stimulated the expression of FXR and BSEP in livers and protected mice from LPS-induced hepatocyte apoptosis and inflammatory infiltration. Consistently, LPS-induced higher serum levels of ALT, AST, TBA and TBIL were significantly reversed by OCA administration. Meanwhile, the mRNA levels of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α) and IL-6 were decreased in livers of mice in LPS + OCA group compared with LPS group. Further investigation indicated that the higher expression of ATF4 and LC3II/I were associated with the protective effect of OCA on LPS-induced liver injury. Orally OCA pretreatment protects mice from LPS-induced liver injury possibly contributed by improved bile acid homeostasis, decreased inflammatory factors and ATF4-mediated autophagy activity in hepatocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Dietary Supplementation with Lactobacillus casei Alleviates Lipopolysaccharide-Induced Liver Injury in a Porcine Model

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    Di Zhao

    2017-11-01

    Full Text Available This study aims to determine whether Lactobacillus casei (L. casei could relieve liver injury in piglets challenged with lipopolysaccharide (LPS. Piglets were randomly allocated into one of the three groups: control, LPS, and L. casei. The control and LPS groups were fed a corn- and soybean meal-based diet, whereas the L. casei group was fed the basal diet supplemented with 6 × 106 cfu/g L. casei. On Day 31 of the trial, piglets in the LPS and L. casei groups received intraperitoneal administration of LPS (100 µg/kg body weight, while the control group received the same volume of saline. Blood and liver samples were collected for analysis. Results showed that L. casei supplementation decreased the feed/gain ratio (p = 0.027 and diarrhea incidence (p < 0.001, and attenuated LPS-induced liver histomorphological abnormalities. Compared with the control group, LPS challenge dramatically increased glutamyl transpeptidase activity (p = 0.001 in plasma as well as the concentrations of Interleukin 6 (IL-6 (p = 0.048, Tumor necrosis factor-alpha (TNF-α (p = 0.041, and Malondialdehyde (MDA (p = 0.001 in the liver, while decreasing the hepatic SOD activity. LPS also increased (p < 0.05 the mRNA levels for IL-6, IL-8, TNF-α, Toll-like receptors 4 (TLR4, Nuclear factor κB (NF-κB and Heat shock protein 70 (HSP70 in the liver. The adverse effects of LPS challenge were ameliorated by L. casei supplementation. In conclusion, dietary L. casei alleviates LPS-induced liver injury via reducing pro-inflammatory cytokines and increasing anti-oxidative capacity.

  3. Cardiac-Specific Overexpression of Catalase Attenuates Lipopolysaccharide-Induced Myocardial Contractile Dysfunction: Role of Autophagy

    OpenAIRE

    Turdi, Subat; Han, Xuefeng; Huff, Anna F.; Roe, Nathan D.; Hu, Nan; Gao, Feng; Ren, Jun

    2012-01-01

    Lipopolysaccharide (LPS) from Gram-negative bacteria is a major initiator of sepsis, leading to cardiovascular collapse. Accumulating evidence has indicated a role of reactive oxygen species (ROS) in cardiovascular complication in sepsis. This study was designed to examine the effect of cardiac-specific overexpression of catalase in LPS-induced cardiac contractile dysfunction and the underlying mechanism(s) with a focus on autophagy. Catalase transgenic and wild-type FVB mice were challenged ...

  4. Improved Hepatoprotective Effect of Liposome-Encapsulated Astaxanthin in Lipopolysaccharide-Induced Acute Hepatotoxicity

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    Chun-Hung Chiu

    2016-07-01

    Full Text Available Lipopolysaccharide (LPS-induced acute hepatotoxicity is significantly associated with oxidative stress. Astaxanthin (AST, a xanthophyll carotenoid, is well known for its potent antioxidant capacity. However, its drawbacks of poor aqueous solubility and low bioavailability have limited its utility. Liposome encapsulation is considered as an effective alternative use for the improvement of bioavailability of the hydrophobic compound. We hypothesized that AST encapsulated within liposomes (LA apparently shows improved stability and transportability compared to that of free AST. To investigate whether LA administration can efficiently prevent the LPS-induced acute hepatotoxicity, male Sprague-Dawley rats (n = six per group were orally administered liposome-encapsulated AST at 2, 5 or 10 mg/kg-day (LA-2, LA-5, and LA-10 for seven days and then were LPS-challenged (i.p., 5 mg/kg. The LA-10 administered group, but not the other groups, exhibited a significant amelioration of serum glutamic pyruvic transaminase (GPT, glutamic oxaloacetic transaminase (GOT, blood urea nitrogen (BUN, creatinine (CRE, hepatic malondialdehyde (MDA and glutathione peroxidase (GSH-Px, IL-6, and hepatic nuclear NF-κB and inducible nitric oxide synthase (iNOS, suggesting that LA at a 10 mg/kg-day dosage renders hepatoprotective effects. Moreover, the protective effects were even superior to that of positive control N-acetylcysteine (NAC, 200 mg/kg-day. Histopathologically, NAC, free AST, LA-2 and LA-5 partially, but LA-10 completely, alleviated the acute inflammatory status. These results indicate that hydrophobic AST after being properly encapsulated by liposomes improves bioavailability and can also function as potential drug delivery system in treating hepatotoxicity.

  5. Magnesium Isoglycyrrhizinate attenuates lipopolysaccharide-induced depressive-like behavior in mice.

    Science.gov (United States)

    Jiang, Wenjiao; Chen, Qianying; Li, Peijin; Lu, Qianfeng; Pei, Xue; Sun, Yilin; Wang, Guangji; Hao, Kun

    2017-02-01

    Magnesium Isoglycyrrhizinate (MI) is a magnesium salt of 18α-GA stereoisomer which has been reported to exert hepatoprotective activity. The aim of the present study was to ascertain the underlying mechanisms behind the action of Magnesium Isoglycyrrhizinate on neuroinflammatation and oxidative stress in LPS-stimulated mice. Mice were pretreated with Magnesium Isoglycyrrhizinate (MI, 25, 50mg/kg) as well as fluoxetine (Flu, positive control, 20mg/kg) once daily for one week before intraperitoneal injection of LPS (0.83mg/kg). Pretreatments with MI and Flu significantly improved immobility time in tail suspension test (TST) and forced swim test (FST) as well as locomotor activity in open-field test (OFT). In addition, the levels of pro-inflammatory cytokines and oxidative stress in serum and hippocampus were also suppressed effectively by MI and Flu administrations. Western blot analysis showed the up-regulated levels of p-Jak3, p-STAT3, p-NF-κBp65, and p-IκBα in mice exposed to LPS, while different degrees of down-regulation in these expression were observed in MI (25, 50mg/kg) and Flu (20mg/kg) groups respectively. Taken together, our obtained results demonstrated that Magnesium Isoglycyrrhizinate (MI) exhibited an antidepressant-like effect in LPS-induced mice, which might be mediated by JAK/STAT/NF-κB signaling pathway. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Lipopolysaccharide-induced metabolome signature in Arabidopsis thaliana reveals dynamic reprogramming of Phytoalexin and Phytoanticipin pathways

    CSIR Research Space (South Africa)

    Finnegan, T

    2016-09-01

    Full Text Available tentatively identified. These include the phytohormones salicylic acid and jasmonic acid, and also the associated methyl esters and sugar conjugates. The induced defensive state resulted in increases in indoleÐand other glucosinolates, indole derivatives...

  7. Valproic acid potentiates curcumin-mediated neuroprotection in Lipopolysaccharide induced rats

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    Amira eZaky

    2014-10-01

    Full Text Available The etiology of neuroinflammation is complex and comprises multifactorial, involving both genetic and environmental factors during which diverse genetic and epigenetic modulations are implicated. Curcumin (Cur, and valproic acid (VPA, histone deacetylase 1 inhibitor, have neuroprotective effects. The present study was designed with an aim to investigate the ability of co-treatment of both compounds (Cur or VPA (200mg/kg for four weeks to augment neuroprotection and enhance brain recovery from intra-peritoneal (IP injection of (250 µg/kg lipopolysaccharide (LPS-stimulated neuroinflammatory condition on rat brain cortex. Cortex activation and the effects of combined treatment and production of proinflammatory mediators, COX-2, APE1 and nitric oxide/iNOS were investigated. Neuroinflammation development was assessed by histological analyses and by investigating associated indices (BACE1, APP, PSEN-1 and PSEN-2. Furthermore we measured the expression profile of let-7 miRNAs members a, b, c, e and f in all groups, a highly abundant regulator of gene expression in the CNS. Protein and mRNA levels of neuroinflammation markers COX-2, BACE1, APP and iNOS were also attenuated by combined therapy. On the other hand, assessment of the indicated five let-7 members, showed distinct expression profile pattern in the different groups. Let-7 a, b and c disappeared in the induced group, an effect that was partially suppressed by co-addition of either Cur or VPA. These data suggest that the combined treatment induced significantly the expression of the five members when compared to rats treated with Cur or VPA only as well as to self-recovery group, which indicates a possible benefit from the synergistic effect of Cur-VPA combination as therapeutic agents for neuroinflammation and its associated disorders. The mechanism elucidated here highlights the particular drug-induced expression profile of let-7 family as new targets for future pharmacological development.

  8. Enriched dairy fat matrix diet prevents early life lipopolysaccharide-induced spatial memory impairment at adulthood.

    Science.gov (United States)

    Dinel, A L; Rey, C; Baudry, C; Fressange-Mazda, C; Le Ruyet, P; Nadjar, A; Pallet, P; Joffre, C; Layé, S

    2016-10-01

    Polyunsaturated fatty acids (PUFAs) are essential fatty acids, which are critical for brain development and later life cognitive functions. The main brain PUFAs are docosahexaenoic acid (DHA) for the n-3 family and arachidonic acid (ARA) for the n-6 family, which are provided to the post-natal brain by breast milk or infant formula. Recently, the use of dairy lipids (DL) in replacement of vegetable lipids (VL) was revealed to potently promote the accretion of DHA in the developing brain. Brain DHA, in addition to be a key component of brain development, display potent anti-inflammatory activities, which protect the brain from adverse inflammatory events. In this work, we evaluated the protective effect of partial replacement of VL by DL, supplemented or not with DHA and ARA, on post-natal inflammation and its consequence on memory. Mice were fed with diets poor in vegetal n-3 PUFA (Def VL), balanced in vegetal n-3/n-6 PUFA (Bal VL), balanced in dairy lipids (Bal DL) or enriched in DHA and ARA (Supp VL; Supp DL) from the first day of gestation until adulthood. At post-natal day 14 (PND14), pups received a single administration of the endotoxin lipopolysaccharide (LPS) and brain cytokine expression, microglia phenotype and neurogenesis were measured. In a second set of experiments, memory and neurogenesis were measured at adulthood. Overall, our data showed that lipid quality of the diet modulates early life LPS effect on microglia phenotype, brain cytokine expression and neurogenesis at PND14 and memory at adulthood. In particular, Bal DL diet protects from the adverse effect of early life LPS exposure on PND14 neurogenesis and adult spatial memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Atomic force microscopy observation of lipopolysaccharide-induced cardiomyocyte cytoskeleton reorganization.

    Science.gov (United States)

    Wang, Liqun; Chen, Tangting; Zhou, Xiang; Huang, Qiaobing; Jin, Chunhua

    2013-08-01

    We applied atomic force microscopy (AFM) to observe lipopolysaccharide (LPS)-induced intracellular cytoskeleton reorganization in primary cardiomyocytes from neonatal mouse. The nonionic detergent Triton X-100 was used to remove the membrane, soluble proteins, and organelles from the cell. The remaining cytoskeleton can then be directly visualized by AFM. Using three-dimensional technique of AFM, we were able to quantify the changes of cytoskeleton by the "density" and total "volume" of the cytoskeleton fibers. Compared to the control group, the density of cytoskeleton was remarkably decreased and the volume of cytoskeleton was significantly increased after LPS treatment, which suggests that LPS may induce the cytoskeleton reorganization and change the cardiomyocyte morphology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Alpha-lipoic acid protects mitochondrial enzymes and attenuates lipopolysaccharide-induced hypothermia in mice

    Science.gov (United States)

    Abstract: Hypothermia is a key symptom of sepsis and the mechanism(s) leading to hypothermia during sepsis is largely unknown. To investigate a potential mechanism and find an effective treatment for hypothermia in sepsis, we induced hypothermia in mice by lipopolysaccharide (LP...

  11. RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

    Directory of Open Access Journals (Sweden)

    Suri SS

    2011-12-01

    Full Text Available Sarabjeet Singh Suri1, Steven Mills1, Gurpreet Kaur Aulakh1, Felaniaina Rakotondradany2, Hicham Fenniri2, Baljit Singh11Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon; 2National Institute for Nanotechnology and Department of Chemistry, Edmonton, CanadaAbstract: Rosette nanotubes (RNT are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif. In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C and amino acid Lys (K-G∧C which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as Kx/RGDSKy-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK–G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous Kx/RGDSKy-RNT on acute lipopolysaccharide (LPS-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 µg and/or intravenously with K90/RGDSK10-RNT. Here we provide the first evidence that intravenous administration of K90/RGDSK10-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K90/RGDSK10-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K90/RGDSK10-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1ß, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K90/RGDSK10-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.Keywords: RGD peptide, helical rosette nanotubes, neutrophils, macrophages, chemokines, inflammation

  12. Methyl jasmonate attenuated lipopolysaccharide-induced depressive-like behaviour in mice.

    Science.gov (United States)

    Adebesin, Adaeze; Adeoluwa, Olusegun A; Eduviere, Anthony T; Umukoro, Solomon

    2017-11-01

    Depression is a recurrent neuropsychiatric disorder that affects millions of individuals worldwide and impact negatively on the patients' social functions and quality of life. Studies have shown that i.p injection of lipopolysaccharide (LPS) induces depressive-like behavior in rodents via induction of oxidative stress and neuroinflammation. Methyl jasmonate (MJ), an isolated compound from jasmine plant has gained reputation in aromatherapy for treatment of depression, nervousness and memory deficits. This study was designed to evaluate the effects of MJ on LPS-induced depressive-like behavior in mice. Mice were given MJ (5-20 mg/kg), imipramine (10 mg/kg) or vehicle (10 mL/kg) intraperitoneally for 7 consecutive days. On day 7, treatment was carried out 30 min prior to i.p injection of LPS (830 μg/kg). Twenty four hours after LPS administration, tail suspension, forced swim and sucrose preference tests were carried out. Thereafter, serum corticosterone levels were determined using ELISA. The levels of malondialdehyde (MDA), glutathione (GSH) and tumor necrosis factor-alpha (TNF-α) were determined in brain tissue homogenates. LPS significantly increased immobility time in the tail suspension and forced swim tests when compared with vehicle (p < 0.05), which indicates depressive-like syndromes. However, the increased immobility time was significantly reduced by MJ (5-20 mg/kg) when compared with LPS-treated group. LPS administration also altered the levels of MDA, GSH, corticosterone and TNF alpha in mice, which was significantly reversed by MJ. These findings suggest that attenuation of LPS-induced depressive-like behavior by MJ may be related to suppression of oxidative stress and release of TNF alpha. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Lipopolysaccharide-induced neuronal activation in the paraventricular and dorsomedial hypothalamus depends on ambient temperature.

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    Samuel P Wanner

    Full Text Available Systemic inflammatory response syndrome is associated with either fever or hypothermia, but the mechanisms responsible for switching from one to the other are unknown. In experimental animals, systemic inflammation is often induced by bacterial lipopolysaccharide (LPS. To identify the diencephalic and brainstem structures involved in the fever-hypothermia switch, we studied the expression of c-Fos protein, a marker of neuronal activation, in rats treated with the same high dose of LPS (0.5 mg/kg, intravenously either in a thermoneutral (30 °C or cool (24 °C environment. At 30 °C, LPS caused fever; at 24 °C, the same dose caused profound hypothermia. Both fever and hypothermia were associated with the induction of c-Fos in many brain areas, including several structures of the anterior preoptic, paraventricular, lateral, and dorsal hypothalamus, the bed nucleus of the stria terminalis, the posterior pretectal nucleus, ventrolateral periaqueductal gray, lateral parabrachial nucleus, area postrema, and nucleus of the solitary tract. Every brain area studied showed a comparable response to LPS at the two different ambient temperatures used, with the exception of two areas: the dorsomedial hypothalamic nucleus (DMH, which we studied together with the adjacent dorsal hypothalamic area (DA, and the paraventricular hypothalamic nucleus (PVH. Both structures had much stronger c-Fos expression during LPS hypothermia than during fever. We propose that PVH and DMH/DA neurons are involved in a circuit, which - depending on the ambient temperature - determines whether the thermoregulatory response to bacterial LPS will be fever or hypothermia.

  14. Peripheral and central mediators of lipopolysaccharide induced suppression of defensive rage behavior in the cat.

    Science.gov (United States)

    Bhatt, S; Bhatt, R S; Zalcman, S S; Siegel, A

    2009-11-10

    Based upon recent findings in our laboratory that cytokines microinjected into the medial hypothalamus or periaqueductal gray (PAG) powerfully modulate defensive rage behavior in cat, the present study determined the effects of peripherally released cytokines following lipopolysaccharide (LPS) challenge upon defensive rage. The study involved initial identification of the effects of peripheral administration of LPS upon defensive rage by electrical stimulation from PAG and subsequent determination of the peripheral and central mechanisms governing this process. The results revealed significant elevation in response latencies for defensive rage from 60 to 300 min, post LPS injection, with no detectable signs of sickness behavior present at 60 min. In contrast, head turning behavior elicited by stimulation of adjoining midbrain sites was not affected by LPS administration, suggesting a specificity of the effects of LPS upon defensive rage. Direct administration of LPS into the medial hypothalamus had no effect on defensive rage, suggesting that the effects of LPS were mediated by peripheral cytokines rather than by any direct actions upon hypothalamic neurons. Complete blockade of the suppressive effects of LPS by peripheral pretreatment with an Anti-tumor necrosis factor-alpha (TNFalpha) antibody but not with an anti- interleukin-1 (IL-1) antibody demonstrated that the effects of LPS were mediated through TNF-alpha rather than through an IL-1 mechanism. A determination of the central mechanisms governing LPS suppression revealed that pretreatment of the medial hypothalamus with PGE(2) or 5-HT(1A) receptor antagonists each completely blocked the suppressive effects of LPS, while microinjections of a TNF-alpha antibody into the medial hypothalamus were ineffective. Microinjections of -Iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) benzamide monohydrochloride (p-MPPI) into lateral hypothalamus (to test for anatomical specificity) had no effect upon LPS induced suppression of defensive rage. The results demonstrate that LPS suppresses defensive rage by acting through peripheral TNF-alpha in periphery and that central effects of LPS suppression of defensive rage are mediated through PGE(2) and 5-HT(1A) receptors in the medial hypothalamus.

  15. Deer Bone Oil Extract Suppresses Lipopolysaccharide-Induced Inflammatory Responses in RAW264.7 Cells.

    Science.gov (United States)

    Choi, Hyeon-Son; Im, Suji; Park, Yooheon; Hong, Ki-Bae; Suh, Hyung Joo

    2016-01-01

    The aim of this study was to investigate the effect of deer bone oil extract (DBOE) on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells. DBOE was fractionated by liquid-liquid extraction to obtain two fractions: methanol fraction (DBO-M) and hexane fraction (DBO-H). TLC showed that DBO-M had relatively more hydrophilic lipid complexes, including unsaturated fatty acids, than DBOE and DBO-H. The relative compositions of tetradecenoyl carnitine, α-linoleic acid, and palmitoleic acid increased in the DBO-M fraction by 61, 38, and 32%, respectively, compared with DBOE. The concentration of sugar moieties was 3-fold higher in the DBO-M fraction than DBOE and DBO-H. DBO-M significantly decreased LPS-induced nitric oxide (NO) production in RAW264.7 cells in a dose-dependent manner. This DBO-M-mediated decrease in NO production was due to downregulation of mRNA and protein levels of inducible nitric oxide synthase (iNOS). In addition, mRNA expression of pro-inflammatory mediators, such as cyclooxygenase (COX-2), interleukin (IL)-1β, and IL-12β, was suppressed by DBO-M. Our data showed that DBO-M, which has relatively higher sugar content than DBOE and DBO-H, could play an important role in suppressing inflammatory responses by controlling pro-inflammatory cytokines and mediators.

  16. Lipopolysaccharide induces a downregulation of adiponectin receptors in-vitro and in-vivo

    Directory of Open Access Journals (Sweden)

    Alison Hall

    2015-11-01

    Full Text Available Background. Adipose tissue contributes to the inflammatory response through production of cytokines, recruitment of macrophages and modulation of the adiponectin system. Previous studies have identified a down-regulation of adiponectin in pathologies characterised by acute (sepsis and endotoxaemia and chronic inflammation (obesity and type-II diabetes mellitus. In this study, we investigated the hypothesis that LPS would reduce adiponectin receptor expression in a murine model of endotoxaemia and in adipoocyte and myocyte cell cultures.Methods. 25 mg/kg LPS was injected intra-peritoneally into C57BL/6J mice, equivalent volumes of normal saline were used in control animals. Mice were killed at 4 or 24 h post injection and tissues harvested. Murine adipocytes (3T3-L1 and myocytes (C2C12 were grown in standard culture, treated with LPS (0.1 µg/ml–10 µg/ml and harvested at 4 and 24 h. RNA was extracted and qPCR was conducted according to standard protocols and relative expression was calculated.Results. After LPS treatment there was a significant reduction after 4 h in gene expression of adipo R1 in muscle and peri-renal fat and of adipo R2 in liver, peri-renal fat and abdominal wall subcutaneous fat. After 24 h, significant reductions were limited to muscle. Cell culture extracts showed varied changes with reduction in adiponectin and adipo R2 gene expression only in adipocytes.Conclusions. LPS reduced adiponectin receptor gene expression in several tissues including adipocytes. This reflects a down-regulation of this anti-inflammatory and insulin-sensitising pathway in response to LPS. The trend towards base line after 24 h in tissue depots may reflect counter-regulatory mechanisms. Adiponectin receptor regulation differs in the tissues investigated.

  17. Computational Topology Based Quantification Of Hepatocytes Nuclei In Lipopolysaccharide-Induced Liver Injury In Mice

    Directory of Open Access Journals (Sweden)

    Rodrigo Rojas Moraleda

    2016-06-01

    The computational topology approach proposed successfully detected hepatocyte cells under several natural variations. We evaluated on a per-pixel basis how the segmentation performs on: i all nuclei in the images, ii big round nuclei considered belonging to hepatocytes cells (accuracy 87.2%, recall 80.3%, and iii nuclei regarded to non-parenchymal cells.  

  18. Differential Involvement of the Suprachiasmatic Nucleus in Lipopolysaccharide-Induced Plasma Glucose and Corticosterone Responses

    NARCIS (Netherlands)

    Kalsbeek, Andries; Liu, Ji; Lei, Jun; Timmermans, Loes; Foppen, Ewout; Cailotto, Cathy; Fliers, Eric

    2012-01-01

    The hypothalamic suprachiasmatic nucleus (SCN) is an essential component of the circadian timing system, and an important determinant of neuroendocrine and metabolic regulation. Recent data indicate a modulatory role for the immune system on the circadian timing system. The authors investigated how

  19. Effects of lipopolysaccharide-induced inflammation on expression of growth-associated genes by corticospinal neurons

    Directory of Open Access Journals (Sweden)

    Lieberman AR

    2006-01-01

    Full Text Available Abstract Background Inflammation around cell bodies of primary sensory neurons and retinal ganglion cells enhances expression of neuronal growth-associated genes and stimulates axonal regeneration. We have asked if inflammation would have similar effects on corticospinal neurons, which normally show little response to spinal cord injury. Lipopolysaccharide (LPS was applied onto the pial surface of the motor cortex of adult rats with or without concomitant injury of the corticospinal tract at C4. Inflammation around corticospinal tract cell bodies in the motor cortex was assessed by immunohistochemistry for OX42 (a microglia and macrophage marker. Expression of growth-associated genes c-jun, ATF3, SCG10 and GAP-43 was investigated by immunohistochemistry or in situ hybridisation. Results Application of LPS induced a gradient of inflammation through the full depth of the motor cortex and promoted c-Jun and SCG10 expression for up to 2 weeks, and GAP-43 upregulation for 3 days by many corticospinal neurons, but had very limited effects on neuronal ATF3 expression. However, many glial cells in the subcortical white matter upregulated ATF3. LPS did not promote sprouting of anterogradely labelled corticospinal axons, which did not grow into or beyond a cervical lesion site. Conclusion Inflammation produced by topical application of LPS promoted increased expression of some growth-associated genes in the cell bodies of corticospinal neurons, but was insufficient to promote regeneration of the corticospinal tract.

  20. Bursopentin (BP5 protects dendritic cells from lipopolysaccharide-induced oxidative stress for immunosuppression.

    Directory of Open Access Journals (Sweden)

    Tao Qin

    Full Text Available Dendritic cells (DCs play a vital role in the regulation of immune-mediated inflammatory diseases. Thus, DCs have been regarded as a major target for the development of immunomodulators. However, oxidative stress could disturb inflammatory regulation in DCs. Here, we examined the effect of bursopentine (BP5, a novel pentapeptide isolated from chicken bursa of fabricius, on the protection of DCs against oxidative stress for immunosuppression. BP5 showed potent protective effects against the lipopolysaccharide (LPS-induced oxidative stress in DCs, including nitric oxide, reactive oxygen species and lipid peroxidation. Furthermore, BP5 elevated the level of cellular reductive status through increasing the reduced glutathione (GSH and the GSH/GSSG ratio. Concomitant with these, the activities of several antioxidative redox enzymes, including glutathione peroxidase (GPx, catalase (CAT and superoxide dismutase (SOD, were obviously enhanced. BP5 also suppressed submucosal DC maturation in the LPS-stimulated intestinal epithelial cells (ECs/DCs coculture system. Finally, we found that heme oxygenase 1 (HO-1 was remarkably upregulated by BP5 in the LPS-induced DCs, and played an important role in the suppression of oxidative stress and DC maturation. These results suggested that BP5 could protect the LPS-activated DCs against oxidative stress and have potential applications in DC-related inflammatory responses.

  1. Toxic waste liquor disposal

    International Nuclear Information System (INIS)

    Burton, W.R.

    1985-01-01

    Toxic waste liquors, especially radio active liquors, are disposed in a sub-zone by feeding down a bore hole a first liquid, then a buffer liquid (e.g. water), then the toxic liquors. Pressure variations are applied to the sub-zone to mix the first liquid and liquors to form gels or solids which inhibit further mixing and form a barrier between the sub-zone and the natural waters in the environment of the sub-zone. In another example the location of the sub-zone is selected so that the environement reacts with the liquors to produce a barrier around the zone. Blind bore holes are used to monitor the sub-zone profile. Materials may be added to the liquor to enhance barrier formation. (author)

  2. Solid waste management

    OpenAIRE

    Srebrenkoska, Vineta; Golomeova, Saska; Zhezhova, Silvana

    2013-01-01

    Waste is unwanted or useless materials from households, industry, agriculture, hospitals. Waste materials in solid state are classified as solid waste. Increasing of the amount of solid waste and the pressure what it has on the environment, impose the need to introduce sustainable solid waste management. Advanced sustainable solid waste management involves several activities at a higher level of final disposal of the waste management hierarchy. Minimal use of material and energy resources ...

  3. Harmful Waste Process

    International Nuclear Information System (INIS)

    Ki, Mun Bong; Lee, Shi Jin; Park, Jun Seok; Yoon, Seok Pyo; Lee, Jae Hyo; Jo, Byeong Ryeol

    2008-08-01

    This book gives descriptions of processing harmful waste, including concerned law and definition of harmful waste, current conditions and generation of harmful waste in Korea, international condition of harmful waste, minimizing of generation of harmful waste, treatment and storage. It also tells of basic science for harmful waste disposal with physics, chemistry, combustion engineering, microbiology and technique of disposal such as physical, chemical, biological process, stabilizing and solidification, incineration and waste in landfill.

  4. Radioactive waste

    International Nuclear Information System (INIS)

    Berkhout, F.

    1991-01-01

    Focusing on radioactive waste management and disposal policies in the United Kingdom, Sweden and the Federal Republic of Germany, this book gives a detailed historical account of the policy process in these three countries, and draws out the implications for theory and public policy. This comparative approach underlines how profoundly different the policy process has been in different countries. By comparing the evolution of policy in three countries, fundamental questions about the formation and resolution of technical decisions under uncertainty are clarified. The analysis of nuclear strategy, the politics of nuclear power, and the shifting emphasis of government regulation redefines the issue of radwaste management and sets it at the heat of the current debate about power, the environment and society. The combination of up-to-date technological assessment with an account of the social and political implications of radwaste management makes'Radioactive Waste'particularly useful to students of environmental studies, geography and public administration. (author)

  5. Radioactive waste

    Energy Technology Data Exchange (ETDEWEB)

    Berkhout, F

    1991-01-01

    Focusing on radioactive waste management and disposal policies in the United Kingdom, Sweden and the Federal Republic of Germany, this book gives a detailed historical account of the policy process in these three countries, and draws out the implications for theory and public policy. This comparative approach underlines how profoundly different the policy process has been in different countries. By comparing the evolution of policy in three countries, fundamental questions about the formation and resolution of technical decisions under uncertainty are clarified. The analysis of nuclear strategy, the politics of nuclear power, and the shifting emphasis of government regulation redefines the issue of radwaste management and sets it at the heat of the current debate about power, the environment and society. The combination of up-to-date technological assessment with an account of the social and political implications of radwaste management makes'Radioactive Waste'particularly useful to students of environmental studies, geography and public administration. (author).

  6. mTOR pathway inhibition prevents neuroinflammation and neuronal death in a mouse model of cerebral palsy.

    Science.gov (United States)

    Srivastava, Isha N; Shperdheja, Jona; Baybis, Marianna; Ferguson, Tanya; Crino, Peter B

    2016-01-01

    Mammalian target of rapamycin (mTOR) pathway signaling governs cellular responses to hypoxia and inflammation including induction of autophagy and cell survival. Cerebral palsy (CP) is a neurodevelopmental disorder linked to hypoxic and inflammatory brain injury however, a role for mTOR modulation in CP has not been investigated. We hypothesized that mTOR pathway inhibition would diminish inflammation and prevent neuronal death in a mouse model of CP. Mouse pups (P6) were subjected to hypoxia-ischemia and lipopolysaccharide-induced inflammation (HIL), a model of CP causing neuronal injury within the hippocampus, periventricular white matter, and neocortex. mTOR pathway inhibition was achieved with rapamycin (an mTOR inhibitor; 5mg/kg) or PF-4708671 (an inhibitor of the downstream p70S6kinase, S6K, 75 mg/kg) immediately following HIL, and then for 3 subsequent days. Phospho-activation of the mTOR effectors p70S6kinase and ribosomal S6 protein and expression of hypoxia inducible factor 1 (HIF-1α) were assayed. Neuronal cell death was defined with Fluoro-Jade C (FJC) and autophagy was measured using Beclin-1 and LC3II expression. Iba-1 labeled, activated microglia were quantified. Neuronal death, enhanced HIF-1α expression, and numerous Iba-1 labeled, activated microglia were evident at 24 and 48 h following HIL. Basal mTOR signaling, as evidenced by phosphorylated-S6 and -S6K levels, was unchanged by HIL. Rapamycin or PF-4,708,671 treatment significantly reduced mTOR signaling, neuronal death, HIF-1α expression, and microglial activation, coincident with enhanced expression of Beclin-1 and LC3II, markers of autophagy induction. mTOR pathway inhibition prevented neuronal death and diminished neuroinflammation in this model of CP. Persistent mTOR signaling following HIL suggests a failure of autophagy induction, which may contribute to neuronal death in CP. These results suggest that mTOR signaling may be a novel therapeutic target to reduce neuronal cell death in

  7. Nuclear waste

    International Nuclear Information System (INIS)

    1988-01-01

    The Department of Energy has proposed a draft plan for investigating the Yucca Mountain, Nevada, site to determine if it suitable for a waste repository. This fact sheet provides information on the status of DOE's and the Nuclear Regulatory Commission's efforts to streamline what NRC expects will be the largest and most complex nuclear-licensing proceeding in history, including the development of an electronic information management system called the Licensing Support System

  8. Waste incineration

    International Nuclear Information System (INIS)

    McCormack, M.D.

    1981-01-01

    As a result of the information gained from retrieval projects, the decision was made to perform an analysis of all the available incinerators to determine which was best suited for processing the INEL waste. A number of processes were evaluated for incinerators currently funded by DOE and for municipal incinerators. Slagging pyrolysis included the processes of three different manufacturers: Andco-Torrax, FLK and Purox

  9. Nuclear waste

    International Nuclear Information System (INIS)

    Anon.

    1983-01-01

    The Koeberg nuclear power station, planned to come on stream in 1984, is expected to save South Africa some six million t/annum of coal, and to contribute some 10 per cent of the country's electricity requirements. The use of nuclear energy will provide for growing national energy needs, and reduce high coal transport costs for power generation at the coast. In the long term, however, it gives rise to the controversial question of nuclear waste storage. The Atomic Energy Corporation of South Africa Ltd (AEC) recently announced the purchase of a site in Namaqualand (NW Cape) for the storage of low-level radioactive waste. The Nuclear Development Corporation of South Africa (Pty) Ltd, (NUCOR) will develop and operate the site. The South African Mining and Engineering Journal interviewed Dr P.D. Toens, manager of the Geology Department and Mr P.E. Moore, project engineer, on the subject of nuclear waste, the reasons behind Nucor's choice of site and the storage method

  10. Radioactive wastes

    International Nuclear Information System (INIS)

    Straub, C.P.

    1975-01-01

    A review is presented on the environmental behavior of radioactive wastes. The management of high-level wastes and waste disposal methods were discussed. Some topics included were ore processing, coagulation, absorption and ion exchange, fixation, ground disposal, flotation, evaporation, transmutation and extraterrestrial disposal. Reports were given of the 226 Ra, 224 Ra and tritium activity in hot springs, 90 Sr concentrations in the groundwater and in White Oak Creek, radionuclide content of algae, grasses and plankton, radionuclides in the Danube River, Hudson River, Pacific Ocean, Atlantic Ocean, Lake Michigan, Columbia River and other surface waters. Analysis showed that 239 Pu was scavenged from Lake Michigan water by phytoplankton and algae by a concentration factor of up to 10,000. Benthic invertebrates and fish showed higher 239 Pu concentrations than did their pelagic counterparts. Concentration factors are also given for 234 Th, 60 Co, Fe and Mr in marine organisms. Two models for predicting the impact of radioactivity in the food chain on man were mentioned. In an accidental release from a light-water power reactor to the ocean, the most important radionuclides discharged were found to be 90 Sr, 137 Cs, 239 Pu and activation products 65 Zr, 59 Fe, and 95 Zr

  11. Nuclear waste

    International Nuclear Information System (INIS)

    1990-06-01

    DOE estimates that disposing of radioactive waste from civilian nuclear power plants and its defense-related nuclear facilities could eventually end up costing $32 billion. To pay for this, DOE collects fees from utilities on electricity generated by nuclear power plants and makes payments from its defense appropriation. This report states that unless careful attention is given to its financial condition, the nuclear waste program is susceptible to future shortfalls. Without a fee increase, the civilian-waste part of the program may already be underfunded by at least $2.4 billion (in discounted 1988 dollars). Also, DOE has not paid its share of cost-about $480 million-nor has it disclosed this liability in its financial records. Indexing the civilian fee to the inflation rate would address one major cost uncertainty. However, while DOE intends to do this at an appropriate time, it does not use a realistic rate of inflation as its most probable scenario in assessing whether that time has arrived

  12. National perspective on waste management

    International Nuclear Information System (INIS)

    Crandall, J.L.

    1980-01-01

    Sources of nuclear wastes are listed and the quantities of these wastes per year are given. Methods of processing and disposing of mining and milling wastes, low-level wastes, decommissioning wastes, high-level wastes, reprocessing wastes, spent fuels, and transuranic wastes are discussed. The costs and safeguards involved in the management of this radioactive wastes are briefly covered in this presentation

  13. Radioactive waste management; the realities as against the myths

    International Nuclear Information System (INIS)

    Williams, I.

    1980-01-01

    Nuclear power generation is now an essential requirement for the mankind in the current energy difficulties. The problem of radioactive waste management is arousing the opposition, but it must not inhibit the utilization of nuclear energy. Radioactive waste management concerns the whole course from its occurrence to its final disposal. The purpose of the management is then to protect absolutely the human beings of present and future generations from the danger of radioactivity. Radioactive wastes are varied much in their kinds and natures. While the management technology is nearly all established, the amounts of wastes are increasing. The following matters are described. Definition of radioactive waste management, fundamental strategies of the management, kinds of radioactive wastes, the present situation of radioactive waste management, and problems in the management. (J.P.N.)

  14. Rethinking the waste hierarchy

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, C; Vigsoe, D [eds.

    2005-03-01

    There is an increasing need to couple environmental and economic considerations within waste management. Consumers and companies alike generate ever more waste. The waste-policy challenges of the future lie in decoupling growth in waste generation from growth in consumption, and in setting priorities for the waste management. This report discusses the criteria for deciding priorities for waste management methods, and questions the current principles of EU waste policies. The basis for the discussion is the so-called waste hierarchy which has dominated the waste policy in the EU since the mid-1970s. The waste hierarchy ranks possible methods of waste management. According to the waste hierarchy, the very best solution is to reduce the amount of waste. After that, reuse is preferred to recycling which, in turn, is preferred to incineration. Disposal at a landfill is the least favourable solution. (BA)

  15. Disposal of hazardous wastes

    International Nuclear Information System (INIS)

    Barnhart, B.J.

    1978-01-01

    The Fifth Life Sciences Symposium entitled Hazardous Solid Wastes and Their Disposal on October 12 through 14, 1977 was summarized. The topic was the passage of the National Resources Conservation and Recovery Act of 1976 will force some type of action on all hazardous solid wastes. Some major points covered were: the formulation of a definition of a hazardous solid waste, assessment of long-term risk, list of specific materials or general criteria to specify the wastes of concern, Bioethics, sources of hazardous waste, industrial and agricultural wastes, coal wastes, radioactive wastes, and disposal of wastes

  16. Other Special Waste

    DEFF Research Database (Denmark)

    Brogaard, Line Kai-Sørensen; Christensen, Thomas Højlund

    2011-01-01

    In addition to the main types of special waste related to municipal solid waste (MSW) mentioned in the previous chapters (health care risk waste, WEEE, impregnated wood, hazardous waste) a range of other fractions of waste have in some countries been defined as special waste that must be handled...... separately from MSW. Some of these other special wastes are briefly described in this chapter with respect to their definition, quantity and composition, and management options. The special wastes mentioned here are batteries, tires, polyvinylchloride (PVC) and food waste....

  17. Disposal of radioactive wastes

    International Nuclear Information System (INIS)

    Blomeke, J.O.

    1979-01-01

    Radioactive waste management and disposal requirements options available are discussed. The possibility of beneficial utilization of radioactive wastes is covered. Methods of interim storage of transuranium wastes are listed. Methods of shipment of low-level and high-level radioactive wastes are presented. Various methods of radioactive waste disposal are discussed

  18. Greening waste management

    CSIR Research Space (South Africa)

    Godfrey, Linda K

    2014-11-01

    Full Text Available ). Countries are moving waste up the waste management hierarchy away from landfilling towards waste prevention, reuse, recycling and recovery. According to the International Solid Waste Association (ISWA, 2012:5), around “70% of the municipal waste produced...

  19. Nuclear waste management

    International Nuclear Information System (INIS)

    1982-12-01

    The subject is discussed, with special reference to the UK, under the headings: radiation; origins of the waste (mainly from nuclear power programme; gas, liquid, solid; various levels of activity); dealing with waste (methods of processing, storage, disposal); high-active waste (storage, vitrification, study of means of eventual disposal); waste management (UK organisation to manage low and intermediate level waste). (U.K.)

  20. Hanford Site annual dangerous waste report: Volume 1, Part 1, Generator dangerous waste report, dangerous waste

    International Nuclear Information System (INIS)

    1994-01-01

    This report contains information on hazardous wastes at the Hanford Site. Information consists of shipment date, physical state, chemical nature, waste description, waste number, weight, and waste designation

  1. Hanford Site annual dangerous waste report: Volume 1, Part 1, Generator dangerous waste report, dangerous waste

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    This report contains information on hazardous wastes at the Hanford Site. Information consists of shipment date, physical state, chemical nature, waste description, waste number, weight, and waste designation.

  2. Transuranic waste management program waste form development

    International Nuclear Information System (INIS)

    Bennett, W.S.; Crisler, L.R.

    1981-01-01

    To ensure that all technology necessary for long term management of transuranic (TRU) wastes is available, the Department of Energy has established the Transuranic Waste Management Program. A principal focus of the program is development of waste forms that can accommodate the very diverse TRU waste inventory and meet geologic isolation criteria. The TRU Program is following two approaches. First, decontamination processes are being developed to allow removal of sufficient surface contamination to permit management of some of the waste as low level waste. The other approach is to develop processes which will allow immobilization by encapsulation of the solids or incorporate head end processes which will make the solids compatible with more typical waste form processes. The assessment of available data indicates that dewatered concretes, synthetic basalts, and borosilicate glass waste forms appear to be viable candidates for immobilization of large fractions of the TRU waste inventory in a geologic repository

  3. Waste treatment

    International Nuclear Information System (INIS)

    Davies, D.; Hooper, E.W.

    1981-01-01

    In the treatment of wastes, such as liquid radioactive effluents, it is known to remove radionuclides by successive in situ precipitation of cobalt sulphide, an hydroxide, barium sulphate and a transition element ferrocyanide, followed by separation of the thereby decontaminated effluent. In this invention, use is made of precipitates such as obtained above in the treatment of further fresh liquid radioactive effluent, when it is found that the precipitates have additional capacity for extracting radionuclides. The resulting supernatant liquor may then be subjected to a further precipitation treatment such as above. Decontamination factors for radionuclides of Ce, Ru, Sr and Cs have been considerably enhanced. (author)

  4. Nuclear waste

    International Nuclear Information System (INIS)

    1992-08-01

    In September 1989, a New York commission charged with choosing a site for a low-level radioactive waste disposal facility announced its intent to conduct limited investigations at five potential sites. In this paper the authors review the commission's site selection process. After discussions with your office, the authors agreed to determine if the commission's consideration and selection of the Taylor North site was consistent with its prescribed procedures for considering offered sites. The authors also agreed to identify technical and other issues that need to be addressed before the final site evaluation and the selection steps can be completed

  5. Waste remediation

    Science.gov (United States)

    Halas, Nancy J.; Nordlander, Peter; Neumann, Oara

    2015-12-29

    A system including a steam generation system and a chamber. The steam generation system includes a complex and the steam generation system is configured to receive water, concentrate electromagnetic (EM) radiation received from an EM radiation source, apply the EM radiation to the complex, where the complex absorbs the EM radiation to generate heat, and transform, using the heat generated by the complex, the water to steam. The chamber is configured to receive the steam and an object, wherein the object is of medical waste, medical equipment, fabric, and fecal matter.

  6. Household hazardous waste

    DEFF Research Database (Denmark)

    Fjelsted, Lotte; Christensen, Thomas Højlund

    2007-01-01

    .) comprised 15-25% and foreign items comprised 10-20%. Water-based paint was the dominant part of the paint waste. The chemical composition of the paint waste and the paint-like waste was characterized by an analysis of 27 substances in seven waste fractions. The content of critical substances was tow......'Paint waste', a part of the 'household hazardous waste', amounting to approximately 5 tonnes was collected from recycling stations in two Danish cities. Sorting and analyses of the waste showed paint waste comprised approximately 65% of the mass, paint-like waste (cleaners, fillers, etc...... and the paint waste was less contaminated with heavy metals than was the ordinary household waste. This may suggest that households no longer need to source-segregate their paint if the household waste is incinerated, since the presence of a small quantity of solvent-based paint will not be harmful when...

  7. Immersed radioactive wastes

    International Nuclear Information System (INIS)

    2017-03-01

    This document presents a brief overview of immersed radioactive wastes worldwide: historical aspects, geographical localization, type of wastes (liquid, solid), radiological activity of immersed radioactive wastes in the NE Atlantic Ocean, immersion sites and monitoring

  8. The temporality of waste

    DEFF Research Database (Denmark)

    Madsen, Katrine Dahl; Jordt Jørgensen, Nanna; Læssøe, Jeppe

    Waste is, indisputably, one of the key issues of environmental concerns of our times. In an environment and sustainability education perspective, waste offers concrete entry points to issues of consumption, sustainability and citizenship. Still, waste education has received relatively little...

  9. Waste Characterization Methods

    Energy Technology Data Exchange (ETDEWEB)

    Vigil-Holterman, Luciana R. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Naranjo, Felicia Danielle [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-02

    This report discusses ways to classify waste as outlined by LANL. Waste Generators must make a waste determination and characterize regulated waste by appropriate analytical testing or use of acceptable knowledge (AK). Use of AK for characterization requires several source documents. Waste characterization documentation must be accurate, sufficient, and current (i.e., updated); relevant and traceable to the waste stream’s generation, characterization, and management; and not merely a list of information sources.

  10. Management of radioactive waste

    International Nuclear Information System (INIS)

    Neerdael, B.; Marivoet, J.; Put, M.; Van Iseghem, P.; Volckaert, G.; Wacquier, W.

    1998-09-01

    The document gives an overview of of different aspects of radioactive waste management in Belgium. The document discusses the radioactive waste inventory in Belgium, the treatment and conditioning of radioactive waste as well as activities related to the characterisation of different waste forms. A separate chapter is dedicated to research and development regarding deep geological disposal of radioactive waste. In the Belgian waste management programme, particular emphasis is on studies for disposal in clay. Main results of these studies are highlighted and discussed

  11. Waste Characterization Methods

    International Nuclear Information System (INIS)

    Vigil-Holterman, Luciana R.; Naranjo, Felicia Danielle

    2016-01-01

    This report discusses ways to classify waste as outlined by LANL. Waste Generators must make a waste determination and characterize regulated waste by appropriate analytical testing or use of acceptable knowledge (AK). Use of AK for characterization requires several source documents. Waste characterization documentation must be accurate, sufficient, and current (i.e., updated); relevant and traceable to the waste stream's generation, characterization, and management; and not merely a list of information sources.

  12. Municipal Solid Waste management

    OpenAIRE

    Mirakovski, Dejan; Hadzi-Nikolova, Marija; Doneva, Nikolinka

    2010-01-01

    Waste management covers newly generated waste or waste from an onging process. When steps to reduce or even eliminate waste are to be considered, it is imperative that considerations should include total oversight, technical and management services of the total process.From raw material to the final product this includes technical project management expertise, technical project review and pollution prevention technical support and advocacy.Waste management also includes handling of waste, in...

  13. Utilisation of solid waste

    Energy Technology Data Exchange (ETDEWEB)

    Balu, K

    1978-07-01

    The prime solution to the present energy crisis is the recovery of latent energy from waste materials, for solid waste contains recoverable energy and it merely needs to be released. The paper is concerned with classification of solid waste, energy content of waste, methods of solid waste disposal, and chemical processing of solid waste. Waste disposal must be performed in situ with energy recovery. Scarcity of available land, pollution problem, and unrecovered latent energy restrict the use of the land-filling method. Pyrolysis is an effective method for the energy recovery and disposal problems. Chemical processing is suitable for the separated cellulosic fraction of the waste material.

  14. Potential for waste reduction

    International Nuclear Information System (INIS)

    Warren, J.L.

    1990-01-01

    The author focuses on wastes considered hazardous under the Resource Conservation and Recovery Act. This chapter discusses wastes that are of interest as well as the factors affecting the quantity of waste considered available for waste reduction. Estimates are provided of the quantities of wastes generated. Estimates of the potential for waste reduction are meaningful only to the extent that one can understand the amount of waste actually being generated. Estimates of waste reduction potential are summarized from a variety of government and nongovernment sources

  15. Waste Transfer Stations

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund

    2011-01-01

    tion and transport is usually the most costly part of any waste management system; and when waste is transported over a considerable distance or for a long time, transferring the waste from the collection vehicles to more efficient transportation may be economically beneficial. This involves...... a transfer station where the transfer takes place. These stations may also be accessible by private people, offering flexibility to the waste system, including facilities for bulky waste, household hazardous waste and recyclables. Waste transfer may also take place on the collection route from small...... describes the main features of waste transfer stations, including some considerations about the economical aspects on when transfer is advisable....

  16. Astrocyte production of the chemokine macrophage inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription

    Directory of Open Access Journals (Sweden)

    Santoro Thomas J

    2005-02-01

    Full Text Available Abstract Background In neuropathological processes associated with neutrophilic infiltrates, such as experimental allergic encephalitis and traumatic injury of the brain, the CXC chemokine, macrophage inflammatory protein-2 (MIP-2 is thought to play a pivotal role in the induction and perpetuation of inflammation in the central nervous system (CNS. The origin of MIP-2 in inflammatory disorders of the brain has not been fully defined but astrocytes appear to be a dominant source of this chemokine. Curcumin is a spice principle in, and constitutes approximately 4 percent of, turmeric. Curcumin's immunomodulating and antioxidant activities suggest that it might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation. Relatively unexplored, but relevant to its potential therapeutic efficacy in neuroinflammatory syndromes is the effect of curcumin on chemokine production. To examine the possibility that curcumin may influence CNS inflammation by mechanisms distinct from its known anti-oxidant activities, we studied the effect of this spice principle on the synthesis of MIP-2 by astrocytes. Methods Primary astrocytes were prepared from neonatal brains of CBA/CaJ mice. The cells were stimulated with lipopolysaccharide in the presence or absence of various amount of curcumin or epigallocatechin gallate. MIP-2 mRNA was analyzed using semi-quantitative PCR and MIP-2 protein production in the culture supernatants was quantified by ELISA. Astrocytes were transfected with a MIP-2 promoter construct, pGL3-MIP-2, and stimulated with lipopolysaccharide in the presence or absence of curcumin. Results The induction of MIP-2 gene expression and the production of MIP-2 protein were inhibited by curcumin. Curcumin also inhibited lipopolysaccharide-induced transcription of the MIP-2 promoter reporter gene construct in primary astrocytes. However MIP-2 gene induction by lipopolysaccharide was not inhibited by another anti

  17. Astrocyte production of the chemokine macrophage inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription.

    Science.gov (United States)

    Tomita, Michiyo; Holman, Brita J; Santoro, Christopher P; Santoro, Thomas J

    2005-02-25

    BACKGROUND: In neuropathological processes associated with neutrophilic infiltrates, such as experimental allergic encephalitis and traumatic injury of the brain, the CXC chemokine, macrophage inflammatory protein-2 (MIP-2) is thought to play a pivotal role in the induction and perpetuation of inflammation in the central nervous system (CNS). The origin of MIP-2 in inflammatory disorders of the brain has not been fully defined but astrocytes appear to be a dominant source of this chemokine.Curcumin is a spice principle in, and constitutes approximately 4 percent of, turmeric. Curcumin's immunomodulating and antioxidant activities suggest that it might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation. Relatively unexplored, but relevant to its potential therapeutic efficacy in neuroinflammatory syndromes is the effect of curcumin on chemokine production. To examine the possibility that curcumin may influence CNS inflammation by mechanisms distinct from its known anti-oxidant activities, we studied the effect of this spice principle on the synthesis of MIP-2 by astrocytes. METHODS: Primary astrocytes were prepared from neonatal brains of CBA/CaJ mice. The cells were stimulated with lipopolysaccharide in the presence or absence of various amount of curcumin or epigallocatechin gallate. MIP-2 mRNA was analyzed using semi-quantitative PCR and MIP-2 protein production in the culture supernatants was quantified by ELISA. Astrocytes were transfected with a MIP-2 promoter construct, pGL3-MIP-2, and stimulated with lipopolysaccharide in the presence or absence of curcumin. RESULTS: The induction of MIP-2 gene expression and the production of MIP-2 protein were inhibited by curcumin. Curcumin also inhibited lipopolysaccharide-induced transcription of the MIP-2 promoter reporter gene construct in primary astrocytes. However MIP-2 gene induction by lipopolysaccharide was not inhibited by another anti-oxidant, epigallocatechin

  18. Package materials, waste form

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    The schedules for waste package development for the various host rocks were presented. The waste form subtask activities were reviewed, with the papers focusing on high-level waste, transuranic waste, and spent fuel. The following ten papers were presented: (1) Waste Package Development Approach; (2) Borosilicate Glass as a Matrix for Savannah River Plant Waste; (3) Development of Alternative High-Level Waste Forms; (4) Overview of the Transuranic Waste Management Program; (5) Assessment of the Impacts of Spent Fuel Disassembly - Alternatives on the Nuclear Waste Isolation System; (6) Reactions of Spent Fuel and Reprocessing Waste Forms with Water in the Presence of Basalt; (7) Spent Fuel Stabilizer Screening Studies; (8) Chemical Interactions of Shale Rock, Prototype Waste Forms, and Prototype Canister Metals in a Simulated Wet Repository Environment; (9) Impact of Fission Gas and Volatiles on Spent Fuel During Geologic Disposal; and (10) Spent Fuel Assembly Decay Heat Measurement and Analysis

  19. Introduction to Waste Management

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund

    2011-01-01

    Solid waste management is as old as human civilization, although only considered an engineering discipline for about one century. The change from the previous focus on public cleansing of the cities to modern waste management was primarily driven by industrialization, which introduced new materials...... and chemicals, dramatically changing the types and composition of waste, and by urbanization making waste management in urban areas a complicated and costly logistic operation. This book focuses on waste that commonly appears in the municipal waste management system. This chapter gives an introduction to modern...... waste management, including issues as waste definition, problems associated with waste, waste management criteria and approaches to waste management. Later chapters introduce aspects of engineering (Chapter 1.2), economics (Chapter 1.3) and regulation (Chapter 1.4)....

  20. Nuclear waste

    International Nuclear Information System (INIS)

    1989-10-01

    The Department of Energy is awarding grants to the state of Nevada for the state's participation in DOE's program to investigate Yucca Mountain as a possible site for the disposal of civilian nuclear waste. This report has found that DOE's financial assistance budget request of $15 million for Nevada's fiscal year 1990 was not based on the amount the state requested but rather was derived by increasing Nevada's grant funds from the previous year in proportion to the increase that DOE requested for its own activities at the Nevada site. DOE's evaluations of Nevada's requests are performed too late to be used in DOE's budget formulation process because Nevada has been applying for financial assistance at about the same time that DOE submits its budget request to Congress

  1. Nuclear waste

    International Nuclear Information System (INIS)

    1991-01-01

    The Privacy Act of 1974 restricts both the type of information on private individuals that federal agencies may maintain in their records and the conditions under which such information may be disclosed. The Nuclear Regulatory Commission, which must approve DOE plans to build a nuclear waste repository at the Yucca Mountain site in Nevada, requires a quality assurance program to guarantee that studies of the site are done by qualified employees. Under such a program, the training and qualifications of DOE and contractor employees would be verified. This report reviews DOE's efforts to identify and resolve the implications of the Privacy Act for DOE's quality assurance program and how the delay in resolving Privacy Act issues may have affected preliminary work on the Yucca Mountain project

  2. Sequential batch anaerobic composting of municipal solid waste (MSW) and yard waste

    Energy Technology Data Exchange (ETDEWEB)

    O' Keefe, D.M.; Chynoweth, D.P.; Barkdoll, A.W.; Nordstedt, R.A.; Owens, J.M.; Sifontes, J. (Florida Univ., Gainesville, FL (United States). Dept. of Agricultural Engineering)

    1993-01-01

    Sequential batch anaerobic composting (SEBAC[sup TM]) was used to treat two fractions of municipal solid waste (MSW), the organic fraction of the MSW (processed MSW) and yard waste. Processed MSW gave a mean methane yield of 0.19 m[sup 3] kg[sup -1] volatile solids (VS) after 42 days. The mean VS reduction was 49.7% for this same period. Yard waste gave a mean methane yield of 0.07 m[sup 3] kg[sup -1] VS. Methane content of the biogas stabilized at a mean of 48% from three to four days after startup. The mean VS reduction for yard waste was 19%. With processed MSW, the volatile acid concentration was over 3000 mg L[sup -1] during startup but these acids were reduced within a few days to negligible levels. The trend was similar with yard waste except that volatile acids reached maximum concentrations of less than 1000 mg L[sup -1]. Composts from the reactors were evaluated for agronomic characteristics and pollution potential. Processed MSW and yard waste residues had marginal fertilizer value but posed no potential for groundwater pollution. Yard waste residue caused no apparent inhibition to mustard (Brassica juncea) germination relative to a commercial growth medium. Anaerobic yard waste compost demonstrated the potential to improve the water holding capacity of Florida soils. (author)

  3. Hanford Site annual dangerous waste report: Volume 3, Part 1, Waste Management Facility report, dangerous waste

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    This report contains information on hazardous wastes at the Hanford Site. Information consists of shipment date, physical state, chemical nature, waste description, handling method and containment vessel, waste number, waste designation, and amount of waste.

  4. Hanford Site annual dangerous waste report: Volume 4, Waste Management Facility report, Radioactive mixed waste

    International Nuclear Information System (INIS)

    1994-01-01

    This report contains information on radioactive mixed wastes at the Hanford Site. Information consists of shipment date, physical state, chemical nature, waste description, handling method and containment vessel, waste number, waste designation and amount of waste

  5. Hanford Site annual dangerous waste report: Volume 2, Generator dangerous waste report, radioactive mixed waste

    International Nuclear Information System (INIS)

    1994-01-01

    This report contains information on radioactive mixed wastes at the Hanford Site. Information consists of shipment date, physical state, chemical nature, waste description, waste number, waste designation, weight, and waste designation

  6. Hanford Site annual dangerous waste report: Volume 3, Part 1, Waste Management Facility report, dangerous waste

    International Nuclear Information System (INIS)

    1994-01-01

    This report contains information on hazardous wastes at the Hanford Site. Information consists of shipment date, physical state, chemical nature, waste description, handling method and containment vessel, waste number, waste designation, and amount of waste

  7. Hanford Site annual dangerous waste report: Volume 3, Part 2, Waste Management Facility report, dangerous waste

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1944-12-31

    This report contains information on hazardous wastes at the Hanford Site. Information consists of shipment date, physical state, chemical nature, waste description, handling and containment vessel, waste number, waste designation and amount of waste.

  8. Waste management, final waste disposal, fuel cycle

    International Nuclear Information System (INIS)

    Rengeling, H.W.

    1991-01-01

    Out of the legal poblems that are currently at issue, individual questions from four areas are dealt with: privatization of ultimate waste disposal; distribution of responsibilities for tasks in the field of waste disposal; harmonization and systematization of regulations; waste disposal - principles for making provisions for waste disposal - proof of having made provisions for waste disposal; financing and fees. A distinction has to be made between that which is legally and in particular constitutionally imperative or, as the case may be, permissible, and issues where there is room for political decision-making. Ultimately, the deliberations on the amendment are completely confined to the sphere of politics. (orig./HSCH) [de

  9. Nuclear wastes, a questionnaire

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    Questionnaire giving basic information for the public on nuclear wastes and radioactive waste management. Risk and regulations to reduce the risk to permissible limits are more particularly developed. A survey of radioactive wastes is made along the fuel cycle: production, processing, transport, disposal to end on effect of waste management on the cost of nuclear kWh [fr

  10. Hazardous Waste Manifest System

    Science.gov (United States)

    EPA’s hazardous waste manifest system is designed to track hazardous waste from the time it leaves the generator facility where it was produced, until it reaches the off-site waste management facility that will store, treat, or dispose of the waste.

  11. Central Waste Complex (CWC) Waste Analysis Plan

    International Nuclear Information System (INIS)

    ELLEFSON, M.D.

    2000-01-01

    The purpose of this waste analysis plan (WAP) is to document the waste acceptance process, sampling methodologies, analytical techniques, and overall processes that are undertaken for waste accepted for storage at the Central Waste Complex (CWC), which is located in the 200 West Area of the Hanford Facility, Richland, Washington. Because dangerous waste does not include the source special nuclear and by-product material components of mixed waste, radionuclides are not within the scope of this document. The information on radionuclides is provided only for general knowledge. This document has been revised to meet the interim status waste analysis plan requirements of Washington Administrative Code (WAC) 173 303-300(5). When the final status permit is issued, permit conditions will be incorporated and this document will be revised accordingly

  12. Nuclear waste management

    International Nuclear Information System (INIS)

    Rodger, W.A.

    1985-01-01

    Most of our activities have always produced waste products of one sort or another. Huxley gives a humorous account of wastes throughout antiquity. So it should come as no surprise that some radioactive materials end up as waste products requiring management and disposal. Public perception of nuclear waste hazards places them much higher on the ''worry scale'' than is justified by the actual hazard involved. While the public perception of these hazards appears to revolve mostly around high-level wastes, there are several other categories of wastes that must also be controlled and managed. The major sources of radioactive wastes are discussed

  13. Infectious waste feed system

    Science.gov (United States)

    Coulthard, E. James

    1994-01-01

    An infectious waste feed system for comminuting infectious waste and feeding the comminuted waste to a combustor automatically without the need for human intervention. The system includes a receptacle for accepting waste materials. Preferably, the receptacle includes a first and second compartment and a means for sealing the first and second compartments from the atmosphere. A shredder is disposed to comminute waste materials accepted in the receptacle to a predetermined size. A trough is disposed to receive the comminuted waste materials from the shredder. A feeding means is disposed within the trough and is movable in a first and second direction for feeding the comminuted waste materials to a combustor.

  14. Radioactive waste processing

    International Nuclear Information System (INIS)

    Dejonghe, P.

    1978-01-01

    This article gives an outline of the present situation, from a Belgian standpoint, in the field of the radioactive wastes processing. It estimates the annual quantity of various radioactive waste produced per 1000 MW(e) PWR installed from the ore mining till reprocessing of irradiated fuels. The methods of treatment concentration, fixation, final storable forms for liquid and solid waste of low activity and for high level activity waste. The storage of radioactive waste and the plutonium-bearing waste treatement are also considered. The estimated quantity of wastes produced for 5450 MW(e) in Belgium and their destination are presented. (A.F.)

  15. Radioactive waste management

    International Nuclear Information System (INIS)

    1984-07-01

    The purpose of this document is to set out the Government's current strategy for the long term in the management of radioactive wastes. It takes account of the latest developments, and will be subject to review in the light of future developments and studies. The subject is discussed under the headings: what are radioactive wastes; who is responsible; what monitoring takes place; disposal as the objective; low-level wastes; intermediate-level wastes; discharges from Sellafield; heat generating wastes; how will waste management systems and procedures be assessed; how much more waste is there going to be in future; conclusion. (U.K.)

  16. Waste Package Lifting Calculation

    International Nuclear Information System (INIS)

    H. Marr

    2000-01-01

    The objective of this calculation is to evaluate the structural response of the waste package during the horizontal and vertical lifting operations in order to support the waste package lifting feature design. The scope of this calculation includes the evaluation of the 21 PWR UCF (pressurized water reactor uncanistered fuel) waste package, naval waste package, 5 DHLW/DOE SNF (defense high-level waste/Department of Energy spent nuclear fuel)--short waste package, and 44 BWR (boiling water reactor) UCF waste package. Procedure AP-3.12Q, Revision 0, ICN 0, calculations, is used to develop and document this calculation

  17. Radioactive mixed waste disposal

    International Nuclear Information System (INIS)

    Jasen, W.G.; Erpenbeck, E.G.

    1993-02-01

    Various types of waste have been generated during the 50-year history of the Hanford Site. Regulatory changes in the last 20 years have provided the emphasis for better management of these wastes. Interpretations of the Atomic Energy Act of 1954 (AEA), the Resource Conservation and Recovery Act of 1976 (RCRA), and the Hazardous and Solid Waste Amendments (HSWA) have led to the definition of radioactive mixed wastes (RMW). The radioactive and hazardous properties of these wastes have resulted in the initiation of special projects for the management of these wastes. Other solid wastes at the Hanford Site include low-level wastes, transuranic (TRU), and nonradioactive hazardous wastes. This paper describes a system for the treatment, storage, and disposal (TSD) of solid radioactive waste

  18. Understanding radioactive waste

    International Nuclear Information System (INIS)

    Murray, R.L.

    1981-12-01

    This document contains information on all aspects of radioactive wastes. Facts are presented about radioactive wastes simply, clearly and in an unbiased manner which makes the information readily accessible to the interested public. The contents are as follows: questions and concerns about wastes; atoms and chemistry; radioactivity; kinds of radiation; biological effects of radiation; radiation standards and protection; fission and fission products; the Manhattan Project; defense and development; uses of isotopes and radiation; classification of wastes; spent fuels from nuclear reactors; storage of spent fuel; reprocessing, recycling, and resources; uranium mill tailings; low-level wastes; transportation; methods of handling high-level nuclear wastes; project salt vault; multiple barrier approach; research on waste isolation; legal requiremnts; the national waste management program; societal aspects of radioactive wastes; perspectives; glossary; appendix A (scientific American articles); appendix B (reference material on wastes)

  19. Understanding radioactive waste

    Energy Technology Data Exchange (ETDEWEB)

    Murray, R.L.

    1981-12-01

    This document contains information on all aspects of radioactive wastes. Facts are presented about radioactive wastes simply, clearly and in an unbiased manner which makes the information readily accessible to the interested public. The contents are as follows: questions and concerns about wastes; atoms and chemistry; radioactivity; kinds of radiation; biological effects of radiation; radiation standards and protection; fission and fission products; the Manhattan Project; defense and development; uses of isotopes and radiation; classification of wastes; spent fuels from nuclear reactors; storage of spent fuel; reprocessing, recycling, and resources; uranium mill tailings; low-level wastes; transportation; methods of handling high-level nuclear wastes; project salt vault; multiple barrier approach; research on waste isolation; legal requiremnts; the national waste management program; societal aspects of radioactive wastes; perspectives; glossary; appendix A (scientific American articles); appendix B (reference material on wastes). (ATT)

  20. Performance of asphalt mixture incorporating recycled waste

    Science.gov (United States)

    Hamid, Nor Baizura; Abdullah, Mohd Ezree; Sanik, Mohd Erwan; Mokhtar, Mardiha; Kaamin, Masiri; Raduan, Rasyidah; Ramli, Mohd Zakwan

    2017-12-01

    Nowadays, the amount of premix waste was increased every year, especially at the batching plants. Normally, the waste materials will be discarded without doing any innovative and effective research about those materials. This situation has become one of the global concerns due to the increasing number of premix waste produced every year. Therefore, the aim of this study is to evaluate the performance of hot mix asphalt (HMA) using premix waste on improving asphalt mixture fatigue behaviour. The method used in this study was Superpave mix design method. The sample conducted in this study were 0%, 10%, 20%, 30%, and 100% of premix waste respectively. For a binder test, the laboratory test conducted were penetration test, softening test and thin film oven test while for the performance test were resilient modulus test and indirect tensile fatigue test. From the laboratory test, the resilient modulus test was conducted with two different temperature which was 25°C and 40°C. The result from that test was 20% of premix waste had higher resilient modulus at that two different temperatures compared to another samples. From that test also shown that the sample at the lower temperature which was 25°C has higher resilient modulus compared to the temperature of 40°C. Indirect tensile fatigue test showed that the 30% of premix waste sample was suitable for the modified asphalt mixture with referring to the maximum deformation and strain for comparison control, 10%,20%, and 100% of premix waste samples. So, it can be concluded that premix waste inhibits great potential as road construction material and suitable for repeated traffic loading.

  1. Municipal Solid Waste Resources

    Energy Technology Data Exchange (ETDEWEB)

    None

    2016-06-01

    Municipal solid waste (MSW) is a source of biomass material that can be utilized for bioenergy production with minimal additional inputs. MSW resources include mixed commercial and residential garbage such as yard trimmings, paper and paperboard, plastics, rubber, leather, textiles, and food wastes. Waste resources such as landfill gas, mill residues, and waste grease are already being utilized for cost-effective renewable energy generation. MSW for bioenergy also represents an opportunity to divert greater volumes of residential and commercial waste from landfills.

  2. Nuclear waste solidification

    Science.gov (United States)

    Bjorklund, William J.

    1977-01-01

    High level liquid waste solidification is achieved on a continuous basis by atomizing the liquid waste and introducing the atomized liquid waste into a reaction chamber including a fluidized, heated inert bed to effect calcination of the atomized waste and removal of the calcined waste by overflow removal and by attrition and elutriation from the reaction chamber, and feeding additional inert bed particles to the fluidized bed to maintain the inert bed composition.

  3. Nuclear waste solidification

    International Nuclear Information System (INIS)

    Bjorklund, W.J.

    1977-01-01

    High level liquid waste solidification is achieved on a continuous basis by atomizing the liquid waste and introducing the atomized liquid waste into a reaction chamber including a fluidized, heated inert bed to effect calcination of the atomized waste and removal of the calcined waste by overflow removal and by attrition and elutriation from the reaction chamber, and feeding additional inert bed particles to the fluidized bed to maintain the inert bed composition

  4. Radium bearing waste disposal

    International Nuclear Information System (INIS)

    Tope, W.G.; Nixon, D.A.; Smith, M.L.; Stone, T.J.; Vogel, R.A.; Schofield, W.D.

    1995-01-01

    Fernald radium bearing ore residue waste, stored within Silos 1 and 2 (K-65) and Silo 3, will be vitrified for disposal at the Nevada Test Site (NTS). A comprehensive, parametric evaluation of waste form, packaging, and transportation alternatives was completed to identify the most cost-effective approach. The impacts of waste loading, waste form, regulatory requirements, NTS waste acceptance criteria, as-low-as-reasonably-achievable principles, and material handling costs were factored into the recommended approach

  5. Radioactive waste treatment

    International Nuclear Information System (INIS)

    Alter, U.

    1988-01-01

    For the Federal Government the safe disposal of waste from nuclear power plants constitutes the precondition for their further operation. The events in the year 1987 about the conditioning and transport of low activity waste and medium activity waste made it clear that it was necessary to intensify state control and to examine the structures in the field of waste disposal. A concept for the control of radioactive waste with negligible heat development (LAW) from nuclear installations is presented. (DG) [de

  6. Mixed waste management options

    International Nuclear Information System (INIS)

    Owens, C.B.; Kirner, N.P.

    1992-01-01

    Currently, limited storage and treatment capacity exists for commercial mixed waste streams. No commercial mixed waste disposal is available, and it has been estimated that if and when commercial mixed waste disposal becomes available, the costs will be high. If high disposal fees are imposed, generators may be willing to apply extraordinary treatment or regulatory approaches to properly dispose of their mixed waste. This paper explores the feasibility of several waste management scenarios and management options. Existing data on commercially generated mixed waste streams are used to identify the realm of mixed waste known to be generated. Each waste stream is evaluated from both a regulatory and technical perspective in order to convert the waste into a strictly low-level radioactive or a hazardous waste. Alternative regulatory approaches evaluated in this paper include a delisting petition) no migration petition) and a treatability variance. For each waste stream, potentially available treatment options are identified that could lead to these variances. Waste minimization methodology and storage for decay are also considered. Economic feasibility of each option is discussed broadly. Another option for mixed waste management that is being explored is the feasibility of Department of Energy (DOE) accepting commercial mixed waste for treatment, storage, and disposal. A study has been completed that analyzes DOE treatment capacity in comparison with commercial mixed waste streams. (author)

  7. Inhibition of lactation.

    Science.gov (United States)

    Llewellyn-Jones, D

    1975-01-01

    The mechanism and hormonal regulation of lactation is explained and illustrated with a schematic representation. Circulating estrogen above a critical amount seems to be the inhibitory factor controlling lactation during pregnancy. Once delivery occurs, the level of estrogen falls, that of prolactin rises, and lactation begins. Nonsuckling can be used to inhibit lactation. Estrogens can also be used to inhibit lactation more quickly and with less pain. The reported association between estrogens and puerperal thromboembolism cannot be considered conclusive due to defects in the reporting studies. There is no reason not to use estrogens in lactation inhibition except for women over 35 who experienced a surgical delivery. Alternative therapy is available for these women. The recently-developed drug, brom-ergocryptine, may replace other methods of lactation inhibition.

  8. Nuclear waste

    International Nuclear Information System (INIS)

    1990-07-01

    The state of Nevada opposed DOE's development of a nuclear waste repository at Yucca Mountain. As a result, disputes have arisen over how Nevada has spent financial assistance provided by DOE to pay the state's repository program costs. This report reviews Nevada's use of about $32 million in grant funds provided by DOE through June 1989 and found that Nevada improperly spent about $1 million. Nevada used as much as $683,000 for lobbying and litigation expenses that were unauthorized or were expressly prohibited by law, court decision, or grant terms; exceeded a legislative spending limit on socioeconomic studies by about $96,000; and used, contrary to grant terms, about $275,000 from one grant period to pay expenses incurred in the prior year. Also, Nevada did not always exercise adequate internal controls over grant funds, such as timely liquidation of funds advanced to contractors. A permissive approach to grant administration by DOE contributed to Nevada's inappropriate use of grant funds

  9. Management of low level waste generated from ISER

    International Nuclear Information System (INIS)

    Mizushina, Tomoyuki

    1987-01-01

    Low level wastes are generated during nuclear power plant operation. In the case of ISER, low level wastes from the reactor are basically the same as of existing light water reactors. Various low level wastes, including solid, liquid and gaseous, are listed and discussed. In normal operation, high-activity wastes are not subjected to any treatment. For contaminated equipment or reactor parts, it may be desirable to transfer most of the activity to liquid phase through an appropriate decontamination procedure. Highly active solid wastes are usually fixed in a solid form through incorporation into either concrete or asphalt as containment material. Decantation and filtration treatments are usually sufficient before dilution and release of liquid wastes into the environment. Except for ordinary gas filtration, there in normally no other treatment. Under certain circumstances, however, it may be important to apply the decay storage before release to the atmosphere. In accidental circumstances, specific filtration is recommended or even sometimes needed. There are some alternatives for storage and-or disposal of low level wastes. In many cases, shallow land burial is chosen as a realistic method for storage and-or disposal of solid waste. In chosing a disposal method, the radiation dose rate from solid wastes or the specific activity should be taken into account. Boric acid is a retarder for cement setting. This effect of boric acid is inhibited by adding a complexing agent before mixing the waste with cement. (Nogami, K.)

  10. Biodegradation testing of TMI-2 EPICOR-II waste forms

    International Nuclear Information System (INIS)

    Rogers, R.D.; McConnell, J.W. Jr.

    1988-06-01

    ASTM biodegradation tests were conducted on waste forms containing high specific activity ion exchange resins from EPICOR-II prefilters. Those tests were part of a program to test waste forms in accordance with the NRC Branch Technical Position on Waste Form. Small waste forms were manufactured using two different solidification agents, Portland Type I-II cement and vinyl ester-styrene (VES). Ion exchange material was taken from two EPICOR-II prefilters; PF-7, which contained all organic material, and PF-20, which contained organic resins and a layer of inorganic zeolites. Test results showed that the VES waste forms supported microbial growth, while cement waste forms did not support that growth. Growth was also observed adjacent to some VES waste forms. Radiation levels found in the ion exchange resins used in this study were not found to inhibit microbial growth. The extent of degradation of the waste forms could not be determined using the ASTM tests specified by the NRC Branch Technical Position on Waste Form. As a result of this work, a different testing methodology is recommended, which would provide direct verification of waste form capabilities. That methodology would evaluate solidification materials without using the ASTM procedures or subsequent compression testing. The proposed tests would provide exposure to a wide range of microbial species, use appropriately sized specimens, provide for possible use of alternate carbon sources, and extend the test length. Degradation would be determined directly by measuring metabolic activity or specimen weight loss. 16 refs., 15 figs., 3 tabs

  11. Comparison of high-solids to liquid anaerobic co-digestion of food waste and green waste.

    Science.gov (United States)

    Chen, Xiang; Yan, Wei; Sheng, Kuichuan; Sanati, Mehri

    2014-02-01

    Co-digestion of food waste and green waste was conducted with six feedstock mixing ratios to evaluate biogas production. Increasing the food waste percentage in the feedstock resulted in an increased methane yield, while shorter retention time was achieved by increasing the green waste percentage. Food waste/green waste ratio of 40:60 was determined as preferred ratio for optimal biogas production. About 90% of methane yield was obtained after 24.5 days of digestion, with total methane yield of 272.1 mL/g VS. Based the preferred ratio, effect of total solids (TS) content on co-digestion of food waste and green waste was evaluated over a TS range of 5-25%. Results showed that methane yields from high-solids anaerobic digestion (15-20% TS) were higher than the output of liquid anaerobic digestion (5-10% TS), while methanogenesis was inhibited by further increasing the TS content to 25%. The inhibition may be caused by organic overloading and excess ammonia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. The Disposal of Hazardous Wastes.

    Science.gov (United States)

    Barnhart, Benjamin J.

    1978-01-01

    The highlights of a symposium held in October, 1977 spotlight some problems and solutions. Topics include wastes from coal technologies, radioactive wastes, and industrial and agricultural wastes. (BB)

  13. Commercial and Institutional Waste

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund; Fruergaard, Thilde

    2011-01-01

    Commercial and institutional waste is primarily from retail (stores), hotels, restaurants, health care (except health risk waste), banks, insurance companies, education, retirement homes, public services and transport. Within some of these sectors, e.g. retail and restaurants, large variations...... are found in terms of which products and services are offered. Available data on unit generation rates and material composition as well as determining factors are discussed in this chapter. The characterizing of commercial and institutional waste is faced with the problem that often only a part of the waste...... is handled in the municipal waste system, where information is easily accessible. An important part of commercial and institutional waste is packaging waste, and enterprises with large quantities of clean paper, cardboard and plastic waste may have their own facilities for baling and storing their waste...

  14. Radioactive waste management

    International Nuclear Information System (INIS)

    Kawakami, Yutaka

    2008-01-01

    Radioactive waste generated from utilization of radioisotopes and each step of the nuclear fuel cycle and decommissioning of nuclear facilities are presented. On the safe management of radioactive waste management, international safety standards are established such as ''The Principles of Radioactive Waste Management (IAEA)'' and T he Joint Convention on the Safety of Radioactive Waste Management . Basic steps of radioactive waste management consist of treatment, conditioning and disposal. Disposal is the final step of radioactive waste management and its safety is confirmed by safety assessment in the licensing process. Safety assessment means evaluation of radiation dose rate caused by radioactive materials contained in disposed radioactive waste. The results of the safety assessment are compared with dose limits. The key issues of radioactive waste disposal are establishment of long term national strategies and regulations for safe management of radioactive waste, siting of repository, continuity of management activities and financial bases for long term, and security of human resources. (Author)

  15. Construction and Demolition Waste

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund; Andersen, L.

    2011-01-01

    Construction and demolition waste (C&D waste) is the waste generated during the building, repair, remodeling or removal of constructions. The constructions can be roads, residential housing and nonresidential buildings. C&D waste has traditionally been considered without any environmental problems...... should be managed accordingly. Another reason is that it has been documented that a large fraction of C&D waste (about 90 %) can be easily recycled and thus can conserve landfill capacity. C&D waste may conveniently be divided into three subcategories: Buildings, roads and excavations. This chapter...

  16. Predisposal Radioactive Waste Management

    International Nuclear Information System (INIS)

    2014-01-01

    Recognition of the importance of the safe management of radioactive waste means that, over the years, many well-established and effective techniques have been developed, and the nuclear industry and governments have gained considerable experience in this field. Minimization of waste is a fundamental principle underpinning the design and operation of all nuclear operations, together with waste reuse and recycling. For the remaining radioactive waste that will be produced, it is essential that there is a well defined plan (called a waste treatment path) to ensure the safe management and ultimately the safe disposal of radioactive waste so as to guarantee the sustainable long term deployment of nuclear technologies

  17. Waste management progress report

    International Nuclear Information System (INIS)

    1997-06-01

    During the Cold War era, when DOE and its predecessor agencies produced nuclear weapons and components, and conducted nuclear research, a variety of wastes were generated (both radioactive and hazardous). DOE now has the task of managing these wastes so that they are not a threat to human health and the environment. This document is the Waste Management Progress Report for the U.S. Department of Energy dated June 1997. This progress report contains a radioactive and hazardous waste inventory and waste management program mission, a section describing progress toward mission completion, mid-year 1997 accomplishments, and the future outlook for waste management

  18. Introduction to Waste Engineering

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund

    2011-01-01

    Solid waste management as introduced in Chapter 1.1 builds in many ways on engineering. Waste engineering here means the skills and ability to understand quantitatively how a waste management system works in such a detail that waste management can be planned, facilities can be designed and sited......) regional plans for waste management, including (3) the selection of main management technologies and siting of facilities, (4) the design of individual technological units and, for example, (5) the operation of recycling schemes within a municipality. This chapter gives an introduction to waste engineering...

  19. Hanford Site annual dangerous waste report: Volume 1, Part 2, Generator dangerous waste report, dangerous waste

    International Nuclear Information System (INIS)

    1994-01-01

    This report contains information on hazardous materials at the Hanford Site. Information consists of shipment date, physical state, chemical nature, waste description, waste number, weight, and waste designation

  20. Hanford Site annual dangerous waste report: Volume 1, Part 2, Generator dangerous waste report, dangerous waste

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    This report contains information on hazardous materials at the Hanford Site. Information consists of shipment date, physical state, chemical nature, waste description, waste number, weight, and waste designation.

  1. Radioactive Waste in Perspective

    International Nuclear Information System (INIS)

    2011-01-01

    Large volumes of hazardous wastes are produced each year, however only a small proportion of them are radioactive. While disposal options for hazardous wastes are generally well established, some types of hazardous waste face issues similar to those for radioactive waste and also require long-term disposal arrangements. The objective of this NEA study is to put the management of radioactive waste into perspective, firstly by contrasting features of radioactive and hazardous wastes, together with their management policies and strategies, and secondly by examining the specific case of the wastes resulting from carbon capture and storage of fossil fuels. The study seeks to give policy makers and interested stakeholders a broad overview of the similarities and differences between radioactive and hazardous wastes and their management strategies. Contents: - Foreword; - Key Points for Policy Makers; - Executive Summary; - Introduction; - Theme 1 - Radioactive and Hazardous Wastes in Perspective; - Theme 2 - The Outlook for Wastes Arising from Coal and from Nuclear Power Generation; - Risk, Perceived Risk and Public Attitudes; - Concluding Discussion and Lessons Learnt; - Strategic Issues for Radioactive Waste; - Strategic Issues for Hazardous Waste; - Case Studies - The Management of Coal Ash, CO 2 and Mercury as Wastes; - Risk and Perceived Risk; - List of Participants; - List of Abbreviations. (authors)

  2. Aspects of radioactive waste management

    International Nuclear Information System (INIS)

    Cutoiu, Dan

    2003-01-01

    The origin and types of radioactive waste, the objective and the fundamental principles of radioactive waste management and the classification of radioactive waste are presented. Problems of the radioactive waste management are analyzed. (authors)

  3. Objectives for radioactive waste packaging

    International Nuclear Information System (INIS)

    Flowers, R.H.

    1982-04-01

    The report falls under the headings: introduction; the nature of radioactive wastes; how to manage radioactive wastes; packaging of radioactive wastes (supervised storage; disposal); waste form evaluation and test requirements (supervised storage; disposal); conclusions. (U.K.)

  4. Hydrothermal waste package interactions with methane-containing basalt groundwater

    International Nuclear Information System (INIS)

    McGrail, B.P.

    1984-01-01

    Hydrothermal waste package interaction tests were conducted with a mixture of crushed glass, basalt, and steel in methane-containing synthetic basalt groundwater. In the absence of gamma radiolysis, methane was found to have little influence on the corrosion behavior of the waste package constituents. Under gamma radiolysis, methane was found to significantly lower the solution oxidation potential when compared to identical tests without methane. In addition, colloidal hydrocarbon polymers that have been produced under the irradiation conditions of these experiments were not formed. The presence of the waste package constituents apparently inhibited the formation of the polymers. However, the mechanism which prevented their formation was not determined

  5. Wastes - Issue 2014. Key figures

    International Nuclear Information System (INIS)

    Haeusler, Laurence; Moro-Goubely, Anne-Gaelle; Berthoin, Guillaume; Mathery, Christian; Galio, Pierre; Heyberger-Paroisse, Agnes

    2014-06-01

    This publication proposes numerous tables and graphs of data and indicators (and of their evolution) regarding wastes. It addresses waste prevention and production in France (concerned materials, waste production, waste origins, actions and measures for waste prevention, re-use), waste collection (for domestic, industrial wastes, cross-border exchanges, nuclear reactors), waste processing (of dangerous and non dangerous wastes), valorisation processes (sorting, recycling, composting, methanization), waste-based energy production, economy and costs of the waste management activity, and environmental impacts (atmospheric emissions, impact of recycling)

  6. ITER waste management

    International Nuclear Information System (INIS)

    Rosanvallon, S.; Na, B.C.; Benchikhoune, M.; Uzan, J. Elbez; Gastaldi, O.; Taylor, N.; Rodriguez, L.

    2010-01-01

    ITER will produce solid radioactive waste during its operation (arising from the replacement of components and from process and housekeeping waste) and during decommissioning (de-activation phase and dismantling). The waste will be activated by neutrons of energies up to 14 MeV and potentially contaminated by activated corrosion products, activated dust and tritium. This paper describes the waste origin, the waste classification as a function of the French national agency for radioactive waste management (ANDRA), the optimization process put in place to reduce the waste radiotoxicity and volumes, the estimated waste amount based on the current design and maintenance procedure, and the overall strategy from component removal to final disposal anticipated at this stage of the project.

  7. Radioactive wastes. Management

    International Nuclear Information System (INIS)

    Guillaumont, R.

    2001-01-01

    Many documents (journal articles, book chapters, non-conventional documents..) deal with radioactive wastes but very often this topic is covered in a partial way and sometimes the data presented are contradictory. The aim of this article is to precise the definition of radioactive wastes and the proper terms to describe this topic. It describes the main guidelines of the management of radioactive wastes, in particular in France, and presents the problems raised by this activity: 1 - goal and stakes of the management; 2 - definition of a radioactive waste; 3 - radionuclides encountered; 4 - radio-toxicity and radiation risks; 5 - French actors of waste production and management; 6 - French classification and management principles; 7 - wastes origin and characteristics; 8 - status of radioactive wastes in France per categories; 9 - management practices; 10 - packages conditioning and fabrication; 11 - storage of wastes; 12 - the French law from December 30, 1991 and the opportunities of new ways of management; 13 - international situation. (J.S.)

  8. Waste disposal: preliminary studies

    International Nuclear Information System (INIS)

    Carvalho, J.F. de.

    1983-01-01

    The problem of high level radioactive waste disposal is analyzed, suggesting an alternative for the final waste disposal from irradiated fuel elements. A methodology for determining the temperature field around an underground disposal facility is presented. (E.G.) [pt

  9. Hanford Waste Vitrification Plant

    International Nuclear Information System (INIS)

    Larson, D.E.; Allen, C.R.; Kruger, O.L.; Weber, E.T.

    1991-10-01

    The Hanford Waste Vitrification Plant (HWVP) is being designed to immobilize pretreated Hanford high-level waste and transuranic waste in borosilicate glass contained in stainless steel canisters. Testing is being conducted in the HWVP Technology Development Project to ensure that adapted technologies are applicable to the candidate Hanford wastes and to generate information for waste form qualification. Empirical modeling is being conducted to define a glass composition range consistent with process and waste form qualification requirements. Laboratory studies are conducted to determine process stream properties, characterize the redox chemistry of the melter feed as a basis for controlling melt foaming and evaluate zeolite sorption materials for process waste treatment. Pilot-scale tests have been performed with simulated melter feed to access filtration for solids removal from process wastes, evaluate vitrification process performance and assess offgas equipment performance. Process equipment construction materials are being selected based on literature review, corrosion testing, and performance in pilot-scale testing. 3 figs., 6 tabs

  10. Business unusual - Waste Act implementation: solid waste

    CSIR Research Space (South Africa)

    Oelofse, Suzanna HH

    2013-08-01

    Full Text Available The preamble to the Waste Act (2008) is very clear that, as a result of this legislation, waste management in South Africa will never be the same again. This should send a clear message that ‘business as usual’ will no longer be sufficient....

  11. Waste canister for storage of nuclear wastes

    Science.gov (United States)

    Duffy, James B.

    1977-01-01

    A waste canister for storage of nuclear wastes in the form of a solidified glass includes fins supported from the center with the tips of the fins spaced away from the wall to conduct heat away from the center without producing unacceptable hot spots in the canister wall.

  12. Mixed Waste Focus Area - Waste form initiative

    International Nuclear Information System (INIS)

    Nakaoka, R.; Waters, R.; Pohl, P.; Roach, J.

    1998-01-01

    The mission of the US Department of Energy's (DOE) Mixed Waste Focus Area (MWFA) is to provide acceptable technologies that enable implementation of mixed waste treatment systems which are developed in partnership with end-users, stakeholders, tribal governments, and regulators. To accomplish this mission, a technical baseline was established in 1996 and revised in 1997. The technical baseline forms the basis for determining which technology development activities will be supported by the MWFA. The primary attribute of the technical baseline is a set of prioritized technical deficiencies or roadblocks related to implementation of mixed waste treatment systems. The Waste Form Initiative (WFI) was established to address an identified technical deficiency related to waste form performance. The primary goal of the WFI was to ensure that the mixed low-level waste (MLLW) treatment technologies being developed, currently used, or planned for use by DOE would produce final waste forms that meet the waste acceptance criteria (WAC) of the existing and/or planned MLLW disposal facilities. The WFI was limited to an evaluation of the disposal requirements for the radioactive component of MLLW. Disposal requirements for the hazardous component are dictated by the Resource Conservation and Recovery Act (RCRA), and were not addressed. This paper summarizes the technical basis, strategy, and results of the activities performed as part of the WFI

  13. Waste canister for storage of nuclear wastes

    International Nuclear Information System (INIS)

    Duffy, J.B.

    1977-01-01

    A waste canister for storage of nuclear wastes in the form of a solidified glass includes fins supported from the center with the tips of the fins spaced away from the wall to conduct heat away from the center without producing unacceptable hot spots in the canister wall. 4 claims, 4 figures

  14. Transport of radioactive wastes

    International Nuclear Information System (INIS)

    Stuller, C.

    2003-01-01

    In this article author describes the system of transport and processing of radioactive wastes from nuclear power of Slovenske elektrarne, plc. It is realized the assurance of transport of liquid and solid radioactive wastes to processing links from places of their formation, or of preliminary storage and consistent transports of treated radioactive wastes fixed in cement matrix of fibre-concrete container into Rebublic storage of radioactive wastes in Mochovce

  15. Solid waste handling

    International Nuclear Information System (INIS)

    Parazin, R.J.

    1995-01-01

    This study presents estimates of the solid radioactive waste quantities that will be generated in the Separations, Low-Level Waste Vitrification and High-Level Waste Vitrification facilities, collectively called the Tank Waste Remediation System Treatment Complex, over the life of these facilities. This study then considers previous estimates from other 200 Area generators and compares alternative methods of handling (segregation, packaging, assaying, shipping, etc.)

  16. Radioactive wastes and discharges

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-07-01

    The guide sets out the radiation safety requirements and limits for the treatment of radioactive waste. They shall be observed when discharging radioactive substances into the atmosphere or sewer system, or when delivering solid, low-activity waste to a landfill site without a separate waste treatment plan. The guide does not apply to the radioactive waste resulting from the utilisation of nuclear energy or natural resources.

  17. Radioactivity and nuclear waste

    International Nuclear Information System (INIS)

    Saas, A.

    1996-01-01

    Radioactive wastes generated by nuclear activities must be reprocessed using specific treatments before packaging, storage and disposal. This digest paper gives first a classification of radioactive wastes according to their radionuclides content activity and half-life, and the amount of wastes from the different categories generated each year by the different industries. Then, the radiotoxicity of nuclear wastes is evaluated according to the reprocessing treatments used and to their environmental management (surface storage or burial). (J.S.)

  18. Radioactive waste management

    International Nuclear Information System (INIS)

    Balek, V.

    1994-01-01

    This booklet is a publication by International Atomic Energy Agency for general awareness of citizens and policy-makers to clarify their concept of nuclear wastes. In a very simple way it tells what is radioactivity, radiations and radioactive wastes. It further hints on various medial and industrial uses of radiations. It discusses about different types of radioactive wastes and radioactive waste management. Status of nuclear power plants in Central and Eastern European countries are also discussed

  19. Radioactive wastes and discharges

    International Nuclear Information System (INIS)

    2000-01-01

    The guide sets out the radiation safety requirements and limits for the treatment of radioactive waste. They shall be observed when discharging radioactive substances into the atmosphere or sewer system, or when delivering solid, low-activity waste to a landfill site without a separate waste treatment plan. The guide does not apply to the radioactive waste resulting from the utilisation of nuclear energy or natural resources

  20. Solid waste combustion for alpha waste incineration

    International Nuclear Information System (INIS)

    Orloff, D.I.

    1981-02-01

    Radioactive waste incinerator development at the Savannah River Laboratory has been augmented by fundamental combustion studies at the University of South Carolina. The objective was to measure and model pyrolysis and combustion rates of typical Savannah River Plant waste materials as a function of incinerator operating conditions. The analytical models developed in this work have been incorporated into a waste burning transient code. The code predicts maximum air requirement and heat energy release as a function of waste type, package size, combustion chamber size, and temperature. Historically, relationships have been determined by direct experiments that did not allow an engineering basis for predicting combustion rates in untested incinerators. The computed combustion rates and burning times agree with measured values in the Savannah River Laboratory pilot (1 lb/hr) and full-scale (12 lb/hr) alpha incinerators for a wide variety of typical waste materials

  1. Rock & Roll : Waste seperation

    NARCIS (Netherlands)

    Beunder, L.; Rem, P.C.; Van Den Berg, R.

    2000-01-01

    Five hundred tonnes of glass, 1 million tonnes of plastic,14 million tonnes of building and demolition waste, 7 million tonnes of household waste, 3 million tonnes of packaging, 3.5 million tonnes of paper and board, and 300,000 old cars. All part of the annual harvest of waste materials in the

  2. Radioactive Wastes. Revised.

    Science.gov (United States)

    Fox, Charles H.

    This publication is one of a series of information booklets for the general public published by the United States Atomic Energy Commission. This booklet deals with the handling, processing and disposal of radioactive wastes. Among the topics discussed are: The Nature of Radioactive Wastes; Waste Management; and Research and Development. There are…

  3. Waste vs Resource Management

    CSIR Research Space (South Africa)

    Oelofse, Suzanna HH

    2014-10-01

    Full Text Available Recent global waste statistics show that in the order of 70% of all municipal waste generated worldwide is disposed at landfill, 11% is treated in thermal and Waste-to-Energy (WtE) facilities and the rest (19%) is recycled or treated by mechanical...

  4. WASTE CONTAINMENT OVERVIEW

    Science.gov (United States)

    BSE waste is derived from diseased animals such as BSE (bovine spongiform encepilopothy, also known as Mad Cow) in cattle and CWD (chronic wasting disease) in deer and elk. Landfilling is examined as a disposal option and this presentation introduces waste containment technology...

  5. Household food waste

    NARCIS (Netherlands)

    Wahlen, S.; Winkel, Thomas

    2017-01-01

    Food waste is debated not only in the light of sustainable consumption in research and policy, but also in the broader public. This article focuses on food waste in household contexts, what is widely believed the end of the food chain. However, household food waste is far more complex and intricate

  6. Radioactive waste management policy

    International Nuclear Information System (INIS)

    Morrison, R.W.

    1983-06-01

    The speaker discusses the development of government policy regarding radioactive waste disposal in Canada, indicates overall policy objectives, and surveys the actual situation with respect to radioactive wastes in Canada. He also looks at the public perceptions of the waste management situation and how they relate to the views of governmental decision makers

  7. Mine waste management

    International Nuclear Information System (INIS)

    Hutchinson, I.P.G.; Ellison, R.D.

    1992-01-01

    This book reports on mine waste management. Topics covered include: Performance review of modern mine waste management units; Mine waste management requirements; Prediction of acid generation potential; Attenuation of chemical constituents; Climatic considerations; Liner system design; Closure requirements; Heap leaching; Ground water monitoring; and Economic impact evaluation

  8. Encapsulation of radioactive waste

    International Nuclear Information System (INIS)

    Pordes, O.; Plows, J.P.

    1980-01-01

    A method is described for encapsulating a particular radioactive waste which consists of suspending the waste in a viscous liquid encapsulating material, of synthetic resin monomers or prepolymers, and setting the encapsulating material by addition or condensation polymerization to form a solid material in which the waste is dispersed. (author)

  9. Radioactive waste repository study

    International Nuclear Information System (INIS)

    1978-11-01

    This is the second part of a report of a preliminary study for AECL. It considers the requirements for an underground waste repository for the disposal of wastes produced by the Canadian Nuclear Fuel Program. The following topics are discussed with reference to the repository: 1) geotechnical assessment, 2) hydrogeology and waste containment, 3) thermal loading and 4) rock mechanics. (author)

  10. Swedish waste management

    International Nuclear Information System (INIS)

    Sandwall, L.

    2004-01-01

    Sweden has a well-functioning organization for managing various types of radioactive waste. There is an interim storage facility for spent nuclear fuel, a final repository for low and intermediate level waste, and a specially-built vessel with transport casks and containers for shipping the radioactive waste between the nuclear installations. (author)

  11. Nuclear wastes; Dechets nucleaires

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-07-01

    Here is made a general survey of the situation relative to radioactive wastes. The different kinds of radioactive wastes and the different way to store them are detailed. A comparative evaluation of the situation in France and in the world is made. The case of transport of radioactive wastes is tackled. (N.C.)

  12. Nuclear waste disposal

    International Nuclear Information System (INIS)

    Schueller, W.

    1976-01-01

    The article cites and summarizes the papers on the topics: economic and ecological importance of waste management, reprocessing of nuclear fuel and recycling of uranium and plutonium, waste management and final storage, transports and organizational aspects of waste management, presented at this symposium. (HR/AK) [de

  13. Radioactive wastes management

    International Nuclear Information System (INIS)

    Albert, Ph.

    1999-01-01

    This article presents the French way to deal with nuclear wastes. 4 categories of radioactive wastes have been defined: 1) very low-level wastes (TFA), 2) low or medium-wastes with short or medium half-life (A), 3) low or medium-level wastes with long half-life (B), and 4) high-level wastes with long half-life (C). ANDRA (national agency for the management of radioactive wastes) manages 2 sites of definitive surface storage (La-Manche and Aube centers) for TFA-wastes. The Aube center allows the storage of A-wastes whose half-life is less than 30 years. This site will receive waste packages for 50 years and will require a regular monitoring for 300 years after its decommissioning. No definitive solutions have been taken for B and C wastes, they are temporarily stored at La Hague processing plant. Concerning these wastes the French parliament will have to take a decision by 2006. At this date and within the framework of the Bataille law (1991), scientific studies concerning the definitive or retrievable storage, the processing techniques (like transmutation) will have been achieved and solutions will be proposed. These studies are numerous, long and complex, they involve fresh knowledge in geology, chemistry, physics,.. and they have implied the setting of underground facilities in order to test and validate solutions in situ. This article presents also the transmutation technique. (A.C.)

  14. Ironing out industrial wastes

    International Nuclear Information System (INIS)

    Valenti, M.

    1996-01-01

    This article describes a hazardous waste treatment known as the catalytic extraction process, which also stabilizes and reduces low-level radioactive wastes to a fraction of their original volume, easing their disposal. It uses molten iron and other metals to convert hazardous wastes into useful materials

  15. International waste management conference

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    This book contains the proceedings of the international waste management conference. Topics covered include: Quality assurance in the OCR WM program; Leading the spirit of quality; Dept. of Energy hazardous waste remedial actions program; management of hazardous waste projects; and System management and quality assurance

  16. Waste disposal package

    Science.gov (United States)

    Smith, M.J.

    1985-06-19

    This is a claim for a waste disposal package including an inner or primary canister for containing hazardous and/or radioactive wastes. The primary canister is encapsulated by an outer or secondary barrier formed of a porous ceramic material to control ingress of water to the canister and the release rate of wastes upon breach on the canister. 4 figs.

  17. Waste inventory, waste characteristics and waste repositories in Japan

    International Nuclear Information System (INIS)

    Shimooka, K.

    1997-01-01

    There are two types of repositories for the low level radioactive wastes in Japan. One is a trench type repository only for concrete debris generated from the dismantling of the research reactor. According to the safety assurance system, Japan Atomic Energy Research Institute (JAERI) has disposed of the concrete debris arose from the dismantling of the Japan Power Demonstration Reactor (JPDR). The other type is the concreted pit with engineered barriers. Rokkasho Low Level Radioactive Waste Disposal Center has this type of repository mainly for the power plant wastes. Japan Nuclear Fuel Ltd. (JNFL) established by electric power companies is the operator of the LLW disposal project. JNFL began the storage operation in 1992 and buried approximately 60,000 drums there. Two hundred thousand drums of uniformly solidified, waste may be buried ultimately. 4 refs, 3 tabs

  18. Solidification of low-level radioactive wastes in masonry cement

    International Nuclear Information System (INIS)

    Zhou, H.; Colombo, P.

    1987-03-01

    Portland cements are widely used as solidification agents for low-level radioactive wastes. However, it is known that boric acid wastes, as generated at pressurized water reactors (PWR's) are difficult to solidify using ordinary portland cements. Waste containing as little as 5 wt % boric acid inhibits the curing of the cement. For this purpose, the suitability of masonry cement was investigated. Masonry cement, in the US consists of 50 wt % slaked lime (CaOH 2 ) and 50 wt % of portland type I cement. Addition of boric acid in molar concentrations equal to or less than the molar concentration of the alkali in the cement eliminates any inhibiting effects. Accordingly, 15 wt % boric acid can be satisfactorily incorporated into masonry cement. The suitability of masonry cement for the solidification of sodium sulfate wastes produced at boiling water reactors (BWR's) was also investigated. It was observed that although sodium sulfate - masonry cement waste forms containing as much as 40 wt % Na 2 SO 4 can be prepared, waste forms with more than 7 wt % sodium sulfate undergo catastrophic failure when exposed to an aqueous environment. It was determined by x-ray diffraction that in the presence of water, the sulfate reacts with hydrated calcium aluminate to form calcium aluminum sulfate hydrate (ettringite). This reaction involves a volume increase resulting in failure of the waste form. Formulation data were identified to maximize volumetric efficiency for the solidification of boric acid and sodium sulfate wastes. Measurement of some of the waste form properties relevant to evaluating the potential for the release of radionuclides to the environment included leachability, compression strengths and chemical interactions between the waste components and masonry cement. 15 refs., 19 figs., 9 tabs

  19. Enzyme inhibition by iminosugars

    DEFF Research Database (Denmark)

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  20. Quorum sensing inhibition

    DEFF Research Database (Denmark)

    Persson, T.; Givskov, Michael Christian; Nielsen, J.

    2005-01-01

    /receptor transcriptional regulator in some clinically relevant Gram-negative bacteria. The present review contains all reported compound types that are currently known to inhibit the QS transcriptional regulator in Gram-negative bacteria. These compounds are sub-divided into two main groups, one comprising structural...

  1. Cooperation for Better Inhibiting.

    Science.gov (United States)

    Novoa, Eva Maria; Ribas de Pouplana, Lluís

    2015-06-18

    Cladosporin is an antimalarial drug that acts as an ATP-mimetic to selectively inhibit Plasmodium lysyl-tRNA synthetase. Using multiple crystal structures, Fang et al. (2015) reveal in this issue of Chemistry & Biology the fascinating mechanism responsible for cladosporin selectivity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Radioactive Waste Management Basis

    International Nuclear Information System (INIS)

    Perkins, B.K.

    2009-01-01

    The purpose of this Radioactive Waste Management Basis is to describe the systematic approach for planning, executing, and evaluating the management of radioactive waste at LLNL. The implementation of this document will ensure that waste management activities at LLNL are conducted in compliance with the requirements of DOE Order 435.1, Radioactive Waste Management, and the Implementation Guide for DOE Manual 435.1-1, Radioactive Waste Management Manual. Technical justification is provided where methods for meeting the requirements of DOE Order 435.1 deviate from the DOE Manual 435.1-1 and Implementation Guide.

  3. Management of solid waste

    Science.gov (United States)

    Thompson, W. T.; Stinton, L. H.

    1980-04-01

    Compliance with the latest regulatory requirements addressing disposal of radioactive, hazardous, and sanitary solid waste criteria in the selection, design, and operation of solid waste management facilities. Due to the state of flux of these regulatory requirements from EPA and NRC, several waste management options were of solid waste. The current regulatory constraints and the design and operational requirements for construction of both storage and disposal facilities for use in management of DOE-ORO solid waste are highlighted. Capital operational costs are included for both disposal and storage options.

  4. Management of solid waste

    International Nuclear Information System (INIS)

    Thompson, W.T.; Stinton, L.H.

    1980-01-01

    Compliance with the latest regulatory requirements addressing disposal of radioactive, hazardous, and sanitary solid waste requires the application of numerous qualitative and quantitative criteria in the selection, design, and operation of solid waste management facilities. Due to the state of flux of these regulatory requirements from EPA and NRC several waste management options were identified as being applicable to the management of the various types of solid waste. This paper highlights the current regulatory constraints and the design and operational requirements for construction of both storage and disposal facilities for use in management of DOE-ORO solid waste. Capital and operational costs are included for both disposal and storage options

  5. Radioactive waste management

    International Nuclear Information System (INIS)

    Slansky, C.M.

    1975-01-01

    High-level radioactive waste is produced at Idaho Chemical Processing Plant (ICPP) during the recovery of spent highly enriched nuclear fuels. Liquid waste is stored safely in doubly contained tanks made of steel. The liquid waste is calcined to a solid and stored safely in a retrievable form in doubly contained underground bins. The calcine can be treated further or left untreated in anticipation of ultimate storage. Fluidized bed calcination has been applied to many kinds of high-level waste. The environmental impact of high-level waste management at the ICcP has been negligible and should continue to be negligible. 13 refs

  6. Management of solid waste

    International Nuclear Information System (INIS)

    Thompson, W.T.; Stinton, L.H.

    1980-01-01

    Compliance with the latest regulatory requirements addressing disposal of radioactive, hazardous, and sanitary solid waste requires the application of numerous qualitative and quantitative criteria in the selection, design, and operation of solid waste management facilities. Due to the state of flux of these regulatory requirements from EPA and NRC, several waste management options were identified as being applicable to the management of the various types of solid waste. This paper highlights the current regulatory constraints and the design and operational requirements for construction of both storage and disposal facilities for use in management of DOE-ORO solid waste. Capital and operational costs are included for both disposal and storage options

  7. Radioactive waste management

    International Nuclear Information System (INIS)

    Morley, F.

    1980-01-01

    A summary is given of the report of an Expert Group appointed in 1976 to consider the 1959 White Paper 'The Control of Radioactive Wastes' in the light of the changes that have taken place since it was written and with the extended remit of examining 'waste management' rather than the original 'waste disposal'. The Group undertook to; review the categories and quantities present and future of radioactive wastes, recommend the principles for the proper management of these wastes, advise whether any changes in practice or statutory controls are necessary and make recommendations. (UK)

  8. Management of solid wastes

    Energy Technology Data Exchange (ETDEWEB)

    Williams, D.J. [University of Queensland, St. Lucia, Qld. (Australia). Dept. of Civil Engineering

    1996-12-31

    This chapter introduces the range of solid waste materials produced in the mining and mineral processing industries, with particular reference to Australia. The waste materials are characterised and their important geotechnical engineering properties are discussed. Disposal management techniques for metalliferous, coal, heavy mineral sand, fly ash and bauxite solid wastes are described. Geo-technical techniques for the management of potential contaminants are presented. Minimisation and utilisation of solid wastes, and the economics of solid waste management, are discussed from the perspectives of policy, planning, costing and rehabilitation. 19 figs., 2 tabs.

  9. Properties of radioactive wastes and waste containers

    International Nuclear Information System (INIS)

    Arora, H.S.; Dayal, R.

    1984-01-01

    Major tasks in this NRC-sponsored program include: (1) an evaluation of the acceptability of low-level solidified wastes with respect to minimizing radionuclide releases after burial; and (2) an assessment of the influence of pertinent environmental stresses on the performance of high-integrity radwaste container (HIC) materials. The waste form performance task involves studies on small-scale laboratory specimens to predict and extrapolate: (1) leachability for extended time periods; (2) leach behavior of full-size forms; (3) performance of waste forms under realistic leaching conditions; and (4) leachability of solidified reactor wastes. The results show that leach data derived from testing of small-scale specimens can be extrapolated to estimate leachability of a full-scale specimen and that radionuclide release data derived from testing of simulants can be employed to predict the release behavior of reactor wastes. Leaching under partially saturated conditions exhibits lower releases of radionuclides than those observed under the conventional IAEA-type or ANS 16.1 leach tests. The HIC assessment task includes the characterization of mechanical properties of Marlex CL-100, a candidate radwaste high density polyethylene material. Tensile strength and creep rupture tests have been carried out to determine the influence of specific waste constituents as well as gamma irradiation on material performance. Emphasis in ongoing tests is being placed on studying creep rupture while the specimens are in contact with a variety of chemicals including radiolytic by-products of irradiated resin wastes. 12 references 6 figures, 2 tables

  10. Waste container and method for containing waste

    International Nuclear Information System (INIS)

    Ono, Akira; Matsushita, Mitsuhiro; Doi, Makoto; Nakatani, Seiichi.

    1990-01-01

    In a waste container, water-proof membranes and rare earth element layers are formed on the inner surface of a steel plate concrete container in which steel plates are embedded. Further, rear earth element detectors are disposed each from the inner side of the steel plate concrete container by way of a pressure pipe to the outer side of the container. As a method for actually containing wastes, when a plurality of vessels in which wastes are fixed are collectively enhoused to the waste container, cussioning materials are attached to the inner surface of the container and wastes fixing containers are stacked successively in a plurality of rows in a bag made of elastic materials. Subsequently, fixing materials are filled and tightly sealed in the waste container. When the waste container thus constituted is buried underground, even if it should be deformed to cause intrusion of rain water to the inside of the container, the rare earth elements in the container dissolved in the rain water can be detected by the detectors, the containers are exchanged before the rain water intruding to the inner side is leached to the surrounding ground, to previously prevent the leakage of radioactive nuclides. (K.M.)

  11. Ten questions on nuclear wastes

    International Nuclear Information System (INIS)

    Guillaumont, R.; Bacher, P.

    2004-01-01

    The authors give explanations and answers to ten issues related to nuclear wastes: when a radioactive material becomes a waste, how radioactive wastes are classified and particularly nuclear wastes in France, what are the risks associated with radioactive wastes, whether the present management of radioactive wastes is well controlled in France, which wastes are raising actual problems and what are the solutions, whether amounts and radio-toxicity of wastes can be reduced, whether all long life radionuclides or part of them can be transmuted, whether geologic storage of final wastes is inescapable, whether radioactive material can be warehoused over long durations, and how the information on radioactive waste management is organised

  12. Solid waste study

    International Nuclear Information System (INIS)

    Ortiz, Paul G.

    1995-01-01

    The purpose of this document is to study the solid waste issues brought about by a Type C Investigation; ''Disposal of Inappropriate Material in the Los Alamos County Landfill'' (May 28, 1993). The study was completed in August 1995 by Coleman Research Corporation, under subcontract number 405810005-Y for Los Alamos National Laboratory (LANL). The study confirmed the issues identified in the Type C investigation, and also ascertained further issues or problems. During the course of this study two incidents involving hazardous waste resulted in the inappropriate disposal of the waste. An accidental spill, on June 8, 1995, at one of Laboratory buildings was not handled correctly, and ended up in the LAC Landfill. Hazardous waste was disposed of in a solid waste container and sent to the Los Alamos County Landfill. An attempt to locate the hazardous waste at the LAC Landfill was not successful. The second incident involving hazardous waste was discovered by the FSS-8, during a random dumpster surveillance. An interim dumpster program managed by FSS-8 discovered hazardous waste and copper chips in the solid waste, on August 9, 1995. The hazardous waste and copper chips would have been transported to the LAC Landfill if the audit team had not brought the problem to the awareness of the facility waste management personnel

  13. Waste Management Technical Manual

    Energy Technology Data Exchange (ETDEWEB)

    Buckingham, J.S. [ed.

    1967-08-31

    This Manual has been prepared to provide a documented compendium of the technical bases and general physical features of Isochem Incorporated`s Waste Management Program. The manual is intended to be used as a means of training and as a reference handbook for use by personnel responsible for executing the Waste Management Program. The material in this manual was assembled by members of Isochem`s Chemical Processing Division, Battelle Northwest Laboratory, and Hanford Engineering Services between September 1965 and March 1967. The manual is divided into the following parts: Introduction, contains a summary of the overall Waste Management Program. It is written to provide the reader with a synoptic view and as an aid in understanding the subsequent parts; Feed Material, contains detailed discussion of the type and sources of feed material used in the Waste Management Program, including a chapter on nuclear reactions and the formation of fission products; Waste Fractionization Plant Processing, contains detailed discussions of the processes used in the Waste Fractionization Plant with supporting data and documentation of the technology employed; Waste Fractionization Plant Product and Waste Effluent Handling, contains detailed discussions of the methods of handling the product and waste material generated by the Waste Fractionization Plant; Plant and Equipment, describes the layout of the Waste Management facilities, arrangement of equipment, and individual equipment pieces; Process Control, describes the instruments and analytical methods used for process control; and Safety describes process hazards and the methods used to safeguard against them.

  14. SOLID WASTE STUDY

    Energy Technology Data Exchange (ETDEWEB)

    PAUL G. ORTIZ - COLEMAN RESEARCH CORP/COMPA INDUSTRIES

    1995-08-01

    The purpose of this document is to study the solid waste issues brought about by a Type C Investigation; ``Disposal of Inappropriate Material in the Los Alamos County Landfill'' (May 28, 1993). The study was completed in August 1995 by Coleman Research Corporation, under subcontract number 405810005-Y for Los Alamos National Laboratory (LANL). The study confirmed the issues identified in the Type C investigation, and also ascertained further issues or problems. During the course of this study two incidents involving hazardous waste resulted in the inappropriate disposal of the waste. An accidental spill, on June 8, 1995, at one of Laboratory buildings was not handled correctly, and ended up in the LAC Landfill. Hazardous waste was disposed of in a solid waste container and sent to the Los Alamos County Landfill. An attempt to locate the hazardous waste at the LAC Landfill was not successful. The second incident involving hazardous waste was discovered by the FSS-8, during a random dumpster surveillance. An interim dumpster program managed by FSS-8 discovered hazardous waste and copper chips in the solid waste, on August 9, 1995. The hazardous waste and copper chips would have been transported to the LAC Landfill if the audit team had not brought the problem to the awareness of the facility waste management personnel.

  15. EPRI waste processing projects

    International Nuclear Information System (INIS)

    Shaw, R.A.

    1987-01-01

    The Electric Power Research Institute (EPRI) manages research for its sponsoring electric utilities in the United States. Research in the area of low level radioactive waste (LLRW) from light water reactors focuses primarily on waste processing within the nuclear power plants, monitoring of the waste packages, and assessments of disposal technologies. Accompanying these areas and complimentary to them is the determination and evaluation of the sources of nuclear power plants radioactive waste. This paper focuses on source characterization of nuclear power plant waste, LLRW processing within nuclear power plants, and the monitoring of these wastes. EPRI's work in waste disposal technology is described in another paper in this proceeding by the same author. 1 reference, 5 figures

  16. Mixed waste: Proceedings

    International Nuclear Information System (INIS)

    Moghissi, A.A.; Blauvelt, R.K.; Benda, G.A.; Rothermich, N.E.

    1993-01-01

    This volume contains the peer-reviewed and edited versions of papers submitted for presentation a the Second International Mixed Waste Symposium. Following the tradition of the First International Mixed Waste Symposium, these proceedings were prepared in advance of the meeting for distribution to participants. The symposium was organized by the Mixed Waste Committee of the American Society of Mechanical Engineers. The topics discussed at the symposium include: stabilization technologies, alternative treatment technologies, regulatory issues, vitrification technologies, characterization of wastes, thermal technologies, laboratory and analytical issues, waste storage and disposal, organic treatment technologies, waste minimization, packaging and transportation, treatment of mercury contaminated wastes and bioprocessing, and environmental restoration. Individual abstracts are catalogued separately for the data base

  17. Tank waste treatment science

    International Nuclear Information System (INIS)

    LaFemina, J.P.; Blanchard, D.L.; Bunker, B.C.; Colton, N.G.; Felmy, A.R.; Franz, J.A.; Liu, J.; Virden, J.W.

    1994-01-01

    Remediation efforts at the U.S. Department of Energy's Hanford Site require that many technical and scientific principles be combined for effectively managing and disposing the variety of wastes currently stored in underground tanks. Based on these principles, pretreatment technologies are being studied and developed to separate waste components and enable the most suitable treatment methods to be selected for final disposal of these wastes. The Tank Waste Treatment Science Task at Pacific Northwest Laboratory is addressing pretreatment technology development by investigating several aspects related to understanding and processing the tank contents. The experimental work includes evaluating the chemical and physical properties of the alkaline wastes, modeling sludge dissolution, and evaluating and designing ion exchange materials. This paper gives some examples of results of this work and shows how these results fit into the overall Hanford waste remediation activities. This work is part of series of projects being conducted for the Tank Waste Remediation System

  18. Radioactive wastes and discharges

    International Nuclear Information System (INIS)

    1993-01-01

    According to the Section 24 of the Finnish Radiation Decree (1512/91), the Finnish Centre for Radiation and Nuclear Safety shall specify the concentration and activity limits and principles for the determination whether a waste can be defined as a radioactive waste or not. The radiation safety requirements and limits for the disposal of radioactive waste are given in the guide. They must be observed when discharging radioactive waste into the atmosphere or sewer system, or when delivering solid low-activity waste to a landfill site without a separate waste disposal plan. The guide does not apply to the radioactive waste resulting from the utilization of nuclear energy of natural resources. (4 refs., 1 tab.)

  19. Nuclear waste landscapes

    International Nuclear Information System (INIS)

    Solomon, B.D.; Cameron, D.M.

    1990-01-01

    In this paper the authors explore the time dimension in nuclear waste disposal, with the hope of untangling future land use issues for a full range of radioactive waste facilities. The longevity and hazards presented by nuclear reactor irradiated (spent) fuel and liquid reprocessing waste are well known. Final repositories for these highly radioactive wastes, to be opened early in the 21st Century, are to be located deep underground in rural locations throughout the developed world. Safety concerns are addressed by engineered and geological barriers containing the waste containers, as well as through geographic isolation from heavily populated areas. Yet nuclear power plants (as well as other applications of atomic energy) produce an abundance of other types of radioactive wastes. These materials are generally known as low level wastes (LLW) in the United States, though their level of longevity and radioactivity can vary dramatically

  20. Low level waste disposal

    International Nuclear Information System (INIS)

    Barthoux, A.

    1985-01-01

    Final disposal of low level wastes has been carried out for 15 years on the shallow land disposal of the Manche in the north west of France. Final participant in the nuclear energy cycle, ANDRA has set up a new waste management system from the production center (organization of the waste collection) to the disposal site including the setting up of a transport network, the development of assessment, additional conditioning, interim storage, the management of the disposal center, records of the location and characteristics of the disposed wastes, site selection surveys for future disposals and a public information Department. 80 000 waste packages representing a volume of 20 000 m 3 are thus managed and disposed of each year on the shallow land disposal. The disposal of low level wastes is carried out according to their category and activity level: - in tumuli for very low level wastes, - in monoliths, a concrete structure, of the packaging does not provide enough protection against radioactivity [fr

  1. Wastes in space

    International Nuclear Information System (INIS)

    2011-01-01

    As human space activities have created more wastes on low and high Earth orbits over the past 50 years than the solar system injected meteorites over billions of years, this report gives an overview of this problem. It identifies the origins of these space debris and wastes (launchers, combustion residues, exploitation wastes, out-of-use satellites, accidental explosions, accidental collisions, voluntary destructions, space erosion), and proposes a stock list of space wastes. Then, it distinguishes the situation for the different orbits: low Earth orbit or LEO (traffic, presence of the International Space Station), medium Earth orbits or MEO (traffic, operating satellites, wastes), geostationary Earth orbit or GEO (traffic, operating satellites, wastes). It also discusses wastes and bacteria present on the moon (due to Apollo missions or to crash tests). It evokes how space and nuclear industry is concerned, and discusses the re-entry issue (radioactive boomerang, metallic boomerang). It also indicates elements of international law

  2. Mixed waste: Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Moghissi, A.A.; Blauvelt, R.K.; Benda, G.A.; Rothermich, N.E. [eds.] [Temple Univ., Philadelphia, PA (United States). Dept. of Environmental Safety and Health

    1993-12-31

    This volume contains the peer-reviewed and edited versions of papers submitted for presentation a the Second International Mixed Waste Symposium. Following the tradition of the First International Mixed Waste Symposium, these proceedings were prepared in advance of the meeting for distribution to participants. The symposium was organized by the Mixed Waste Committee of the American Society of Mechanical Engineers. The topics discussed at the symposium include: stabilization technologies, alternative treatment technologies, regulatory issues, vitrification technologies, characterization of wastes, thermal technologies, laboratory and analytical issues, waste storage and disposal, organic treatment technologies, waste minimization, packaging and transportation, treatment of mercury contaminated wastes and bioprocessing, and environmental restoration. Individual abstracts are catalogued separately for the data base.

  3. Thermal plasma waste treatment

    International Nuclear Information System (INIS)

    Heberlein, Joachim; Murphy, Anthony B

    2008-01-01

    Plasma waste treatment has over the past decade become a more prominent technology because of the increasing problems with waste disposal and because of the realization of opportunities to generate valuable co-products. Plasma vitrification of hazardous slags has been a commercial technology for several years, and volume reduction of hazardous wastes using plasma processes is increasingly being used. Plasma gasification of wastes with low negative values has attracted interest as a source of energy and spawned process developments for treatment of even municipal solid wastes. Numerous technologies and approaches exist for plasma treatment of wastes. This review summarizes the approaches that have been developed, presents some of the basic physical principles, provides details of some specific processes and considers the advantages and disadvantages of thermal plasmas in waste treatment applications. (topical review)

  4. Handbook of hazardous waste management

    International Nuclear Information System (INIS)

    Metry, A.A.

    1980-01-01

    The contents of this work are arranged so as to give the reader a detailed understanding of the elements of hazardous waste management. Generalized management concepts are covered in Chapters 1 through 5 which are entitled: Introduction, Regulations Affecting Hazardous Waste Management, Comprehensive Hazardous Waste Management, Control of Hazardous Waste Transportation, and Emergency Hazardous Waste Management. Chapters 6 through 11 deal with treatment concepts and are entitled: General Considerations for Hazardous Waste Management Facilities, Physical Treatment of Hazardous Wastes, Chemical Treatment of Hazardous Wastes, Biological Treatment of Hazardous Wastes, Incineration of Hazardous Wastes, and Hazardous Waste Management of Selected Industries. Chapters 12 through 15 are devoted to ultimate disposal concepts and are entitled: Land Disposal Facilities, Ocean Dumping of Hazardous Wastes, Disposal of Extremely Hazardous Wastes, and Generalized Criteria for Hazardous Waste Management Facilities

  5. Plastics for corrosion inhibition

    CERN Document Server

    Goldade, Victor A; Makarevich, Anna V; Kestelman, Vladimir N

    2005-01-01

    The development of polymer composites containing inhibitors of metal corrosion is an important endeavour in modern materials science and technology. Corrosion inhibitors can be located in a polymer matrix in the solid, liquid or gaseous phase. This book details the thermodynamic principles for selecting these components, their compatibility and their effectiveness. The various mechanisms of metal protection – barrier, inhibiting and electromechanical – are considered, as are the conflicting requirements placed on the structure of the combined material. Two main classes of inhibited materials (structural and films/coatings) are described in detail. Examples are given of structural plastics used in friction units subjected to mechano-chemical wear and of polymer films/coatings for protecting metal objects against corrosion.

  6. Inhibiting the inevitable

    DEFF Research Database (Denmark)

    Shashoua, Yvonne

    2006-01-01

    conservation is to ‘buy time’ for the object. Inhibitive conservation of plastics involves the removal or reduction of factors causing or accelerating degradation including light, oxygen, acids, relative humidity and acidic breakdown products. Specific approaches to conservation have been developed......Once plastics objects are registered in museum collections, the institution becomes responsible for their long term preservation, until the end of their useful lifetime. Plastics appear to deteriorate faster than other materials in museum collections and have a useful lifetime between 5 and 25...... years. Preventive or inhibitive conservation involves controlling the environments in which objects are placed during storage and display, with the aim of slowing the major deterioration reactions. Once in progress, degradation of plastics cannot be stopped or reversed, so the aim of preventive...

  7. Waste management: products and services

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    A number of products and services related to radioactive waste management are described. These include: a portable cement solidification system for waste immobilization; spent fuel storage racks; storage and transport flasks; an on-site low-level waste storage facility; supercompactors; a mobile waste retrieval and encapsulation plant; underwater crushers; fuel assembly disposal; gaseous waste management; environmental restoration and waste management services; a waste treatment consultancy. (UK)

  8. New Waste Calcining Facility (NWCF) Waste Streams

    International Nuclear Information System (INIS)

    K. E. Archibald

    1999-01-01

    This report addresses the issues of conducting debris treatment in the New Waste Calcine Facility (NWCF) decontamination area and the methods currently being used to decontaminate material at the NWCF

  9. Properties of radioactive wastes and waste containers

    International Nuclear Information System (INIS)

    Morcos, N.; Dayal, R.

    1982-01-01

    This program is sponsored by the Nuclear Regulatory Commission to address basic concerns in assessing the performance of solidified radwaste. Experiments were initiated to address these concerns. In particular, leachability of solidified radwastes and the physical stability of the ensuing waste forms were evaluated. In addition, leaching experiments designed to address the effects of alternating wet/dry cycles and of varying the length of these cycles on the leach behavior of waste forms were initiated

  10. Radioactive waste management solutions

    International Nuclear Information System (INIS)

    Siemann, Michael

    2015-01-01

    One of the more frequent questions that arise when discussing nuclear energy's potential contribution to mitigating climate change concerns that of how to manage radioactive waste. Radioactive waste is produced through nuclear power generation, but also - although to a significantly lesser extent - in a variety of other sectors including medicine, agriculture, research, industry and education. The amount, type and physical form of radioactive waste varies considerably. Some forms of radioactive waste, for example, need only be stored for a relatively short period while their radioactivity naturally decays to safe levels. Others remain radioactive for hundreds or even hundreds of thousands of years. Public concerns surrounding radioactive waste are largely related to long-lived high-level radioactive waste. Countries around the world with existing nuclear programmes are developing longer-term plans for final disposal of such waste, with an international consensus developing that the geological disposal of high-level waste (HLW) is the most technically feasible and safe solution. This article provides a brief overview of the different forms of radioactive waste, examines storage and disposal solutions, and briefly explores fuel recycling and stakeholder involvement in radioactive waste management decision making

  11. Radioactive waste management

    International Nuclear Information System (INIS)

    Blomek, D.

    1980-01-01

    The prospects of nuclear power development in the USA up to 2000 and the problems of the fuel cycle high-level radioactive waste processing and storage are considered. The problems of liquid and solidified radioactive waste transportation and their disposal in salt deposits and other geologic formations are discussed. It is pointed out that the main part of the high-level radioactive wastes are produced at spent fuel reprocessing plants in the form of complex aqueous mixtures. These mixtures contain the decay products of about 35 isotopes which are the nuclear fuel fission products, about 18 actinides and their daughter products as well as corrosion products of fuel cans and structural materials and chemical reagents added in the process of fuel reprocessing. The high-level radioactive waste management includes the liquid waste cooling which is necessary for the short and middle living isotope decay, separation of some most dangerous components from the waste mixture, waste solidification, their storage and disposal. The conclusion is drawn that the seccessful solution of the high-level radioactive waste management problem will permit to solve the problem of the fuel cycle radioactive waste management as a whole. The salt deposits, shales and clays are the most suitable for radioactive waste disposal [ru

  12. Waste management in NUCEF

    International Nuclear Information System (INIS)

    Suzuki, Y.; Maeda, A.; Sugikawa, S.; Takeshita, I.

    2000-01-01

    In the NUCEF, the researches on criticality safety have been performed at two critical experiment facilities, STACY and TRACY in addition to the researches on fuel cycle such as advanced reprocessing and partitioning in alpha-gamma concrete cells and glove boxes. Many kinds of radioactive wastes have been generated through the research activities. Furthermore, the waste treatment itself may produce some secondary wastes. In addition, the separation and purification of plutonium of several tens-kg from MOX powder are scheduled in order to supply plutonium nitrate solution fuel for critical experiments at STACY. A large amount of wastes containing plutonium and americium will be generated from the plutonium fuel treatment. From the viewpoint of safety, the proper waste management is one of important works in NUCEF. Many efforts, therefore, have been made for the development of advanced waste treatment techniques to improve the waste management in NUCEF. Especially the reduction of alpha-contaminated wastes is a major interest. For example, the separation of americium is planned from the liquid waste evolved alter plutonium purification by application of tannin gel as an adsorbent of actinide elements. The waste management and the relating technological development in NUCEF are briefly described in this paper. (authors)

  13. Waste management in NUCEF

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Y.; Maeda, A.; Sugikawa, S.; Takeshita, I. [Japan Atomic Energy Research Institute, Dept. of Safety Research Technical Support, Tokai-Mura, Naka-Gun, Ibaraki-Ken (Japan)

    2000-07-01

    In the NUCEF, the researches on criticality safety have been performed at two critical experiment facilities, STACY and TRACY in addition to the researches on fuel cycle such as advanced reprocessing and partitioning in alpha-gamma concrete cells and glove boxes. Many kinds of radioactive wastes have been generated through the research activities. Furthermore, the waste treatment itself may produce some secondary wastes. In addition, the separation and purification of plutonium of several tens-kg from MOX powder are scheduled in order to supply plutonium nitrate solution fuel for critical experiments at STACY. A large amount of wastes containing plutonium and americium will be generated from the plutonium fuel treatment. From the viewpoint of safety, the proper waste management is one of important works in NUCEF. Many efforts, therefore, have been made for the development of advanced waste treatment techniques to improve the waste management in NUCEF. Especially the reduction of alpha-contaminated wastes is a major interest. For example, the separation of americium is planned from the liquid waste evolved alter plutonium purification by application of tannin gel as an adsorbent of actinide elements. The waste management and the relating technological development in NUCEF are briefly described in this paper. (authors)

  14. Mixed Waste Management Facility

    International Nuclear Information System (INIS)

    Brummond, W.; Celeste, J.; Steenhoven, J.

    1993-08-01

    The DOE has developed a National Mixed Waste Strategic Plan which calls for the construction of 2 to 9 mixed waste treatment centers in the Complex in the near future. LLNL is working to establish an integrated mixed waste technology development and demonstration system facility, the Mixed Waste Management Facility (MWMF), to support the DOE National Mixed Waste Strategic Plan. The MWMF will develop, demonstrate, test, and evaluate incinerator-alternatives which will comply with regulations governing the treatment and disposal of organic mixed wastes. LLNL will provide the DOE with engineering data for design and operation of new technologies which can be implemented in their mixed waste treatment centers. MWMF will operate under real production plant conditions and process samples of real LLNL mixed waste. In addition to the destruction of organic mixed wastes, the development and demonstration will include waste feed preparation, material transport systems, aqueous treatment, off-gas treatment, and final forms, thus making it an integrated ''cradle to grave'' demonstration. Technologies from offsite as well as LLNL's will be tested and evaluated when they are ready for a pilot scale demonstration, according to the needs of the DOE

  15. Japanese Nuclear Waste Avatars

    International Nuclear Information System (INIS)

    Wynn Kirby, Peter; Stier, Daniel

    2016-01-01

    Japan's cataclysmic 2011 tsunami has become a vast, unwanted experiment in waste management. The seismic event and resulting Fukushima Daiichi radiation crisis created an awkwardly fortuitous rupture in Japanese nuclear practice that exposed the lax and problematic management of nuclear waste in this country to broader scrutiny, as well as distortions in its very conception. This article looks at the full spectrum of nuclear waste in post-tsunami Japan, from spent fuel rods to contorted reactor containment, and the ways that nuclear waste mirrors or diverges from more quotidian waste practices in Japanese culture. Significantly, the Fukushima Daiichi plant itself and its erstwhile banal surroundings have themselves transmuted into an unwieldy form of nuclear waste. The immense challenges of the Fukushima Daiichi site have stimulated a series of on-the-fly innovations that furnish perspective on more everyday nuclear waste practices in the industry. While some HLW can be reprocessed for limited use in today's reactors, it cannot be ignored that much of Japan's nuclear waste is simply converted into other forms of waste. In a society that has long been fixated on segregating filth, maintaining (imagined) purity, and managing proximity to pollution, the specter of nuclear waste looms over contemporary Japan and its ongoing debates over resources, risk, and Japanese nuclear identity itself

  16. Ferrocyanide tank waste stability

    International Nuclear Information System (INIS)

    Fowler, K.D.

    1993-01-01

    Ferrocyanide wastes were generated at the Hanford Site during the mid to late 1950s as a result of efforts to create more tank space for the storage of high-level nuclear waste. The ferrocyanide process was developed to remove 137 CS from existing waste and newly generated waste that resulted from the recovery of valuable uranium in Hanford Site waste tanks. During the course of research associated with the ferrocyanide process, it was recognized that ferrocyanide materials, when mixed with sodium nitrate and/or sodium nitrite, were capable of violent exothermic reaction. This chemical reactivity became an issue in the 1980s, when safety issues associated with the storage of ferrocyanide wastes in Hanford Site tanks became prominent. These safety issues heightened in the late 1980s and led to the current scrutiny of the safety issues associated with these wastes, as well as current research and waste management programs. Testing to provide information on the nature of possible tank reactions is ongoing. This document supplements the information presented in Summary of Single-Shell Tank Waste Stability, WHC-EP-0347, March 1991 (Borsheim and Kirch 1991), which evaluated several issues. This supplement only considers information particular to ferrocyanide wastes

  17. Waste Inspection Tomography (WIT)

    International Nuclear Information System (INIS)

    Bernardi, R.T.

    1995-01-01

    Waste Inspection Tomography (WIT) provides mobile semi-trailer mounted nondestructive examination (NDE) and assay (NDA) for nuclear waste drum characterization. WIT uses various computed tomography (CT) methods for both NDE and NDA of nuclear waste drums. Low level waste (LLW), transuranic (TRU), and mixed radioactive waste can be inspected and characterized without opening the drums. With externally transmitted x-ray NDE techniques, WIT has the ability to identify high density waste materials like heavy metals, define drum contents in two- and three-dimensional space, quantify free liquid volumes through density and x-ray attenuation coefficient discrimination, and measure drum wall thickness. With waste emitting gamma-ray NDA techniques, WIT can locate gamma emitting radioactive sources in two- and three-dimensional space, identify gamma emitting isotopic species, identify the external activity levels of emitting gamma-ray sources, correct for waste matrix attenuation, provide internal activity approximations, and provide the data needed for waste classification as LLW or TRU. The mobile feature of WIT allows inspection technologies to be brought to the nuclear waste drum storage site without the need to relocate drums for safe, rapid, and cost-effective characterization of regulated nuclear waste. The combination of these WIT characterization modalities provides the inspector with an unprecedented ability to non-invasively characterize the regulated contents of waste drums as large as 110 gallons, weighing up to 1,600 pounds. Any objects that fit within these size and weight restrictions can also be inspected on WIT, such as smaller waste bags and drums that are five and thirty-five gallons

  18. Stabilization of compactible waste

    International Nuclear Information System (INIS)

    Franz, E.M.; Heiser, J.H. III; Colombo, P.

    1990-09-01

    This report summarizes the results of series of experiments performed to determine the feasibility of stabilizing compacted or compactible waste with polymers. The need for this work arose from problems encountered at disposal sites attributed to the instability of this waste in disposal. These studies are part of an experimental program conducted at Brookhaven National Laboratory (BNL) investigating methods for the improved solidification/stabilization of DOE low-level wastes. The approach taken in this study was to perform a series of survey type experiments using various polymerization systems to find the most economical and practical method for further in-depth studies. Compactible dry bulk waste was stabilized with two different monomer systems: styrene-trimethylolpropane trimethacrylate (TMPTMA) and polyester-styrene, in laboratory-scale experiments. Stabilization was accomplished by wetting or soaking compactible waste (before or after compaction) with monomers, which were subsequently polymerized. Three stabilization methods are described. One involves the in-situ treatment of compacted waste with monomers in which a vacuum technique is used to introduce the binder into the waste. The second method involves the alternate placement and compaction of waste and binder into a disposal container. In the third method, the waste is treated before compaction by wetting the waste with the binder using a spraying technique. A series of samples stabilized at various binder-to-waste ratios were evaluated through water immersion and compression testing. Full-scale studies were conducted by stabilizing two 55-gallon drums of real compacted waste. The results of this preliminary study indicate that the integrity of compacted waste forms can be readily improved to ensure their long-term durability in disposal environments. 9 refs., 10 figs., 2 tabs

  19. TSA waste stream and final waste form composition

    International Nuclear Information System (INIS)

    Grandy, J.D.; Eddy, T.L.; Anderson, G.L.

    1993-01-01

    A final vitrified waste form composition, based upon the chemical compositions of the input waste streams, is recommended for the transuranic-contaminated waste stored at the Transuranic Storage Area of the Radioactive Waste Management Complex at the Idaho National Engineering Laboratory. The quantities of waste are large with a considerable uncertainty in the distribution of various waste materials. It is therefore impractical to mix the input waste streams into an ''average'' transuranic-contaminated waste. As a result, waste stream input to a melter could vary widely in composition, with the potential of affecting the composition and properties of the final waste form. This work examines the extent of the variation in the input waste streams, as well as the final waste form under conditions of adding different amounts of soil. Five prominent Rocky Flats Plant 740 waste streams are considered, as well as nonspecial metals and the ''average'' transuranic-contaminated waste streams. The metals waste stream is the most extreme variation and results indicate that if an average of approximately 60 wt% of the mixture is soil, the final waste form will be predominantly silica, alumina, alkaline earth oxides, and iron oxide. This composition will have consistent properties in the final waste form, including high leach resistance, irrespective of the variation in waste stream. For other waste streams, much less or no soil could be required to yield a leach resistant waste form but with varying properties

  20. Advanced liquid waste processing technologies: Theoretical versus actual application

    International Nuclear Information System (INIS)

    Barker, Tracy A.

    1992-01-01

    This paper provides an overview of Chem-Nuclear Systems, Inc. (CNSI) experience with turn-key chromate removal at the Maine Yankee Nuclear Plant. Theoretical and actual experiences are addressed on topics such as processing duration, laboratory testing, equipment requirements, chromate removal, waste generation, and waste processing. Chromate salts are used in industrial recirculation cooling water systems as a corrosion inhibitor. However, chromates are toxic at concentrations necessary for surface inhibition. As a result, Chem-Nuclear was contracted to perform turn-key chromate removal and waste disposal by demineralization. This project was unique in that prior to on-site mobilization, a composite sample of chromated waste was shipped to CNSI laboratories for treatment through a laboratory scale system. Removal efficiency, process media requirements, and waste processing methodology were determined from this laboratory testing. Samples of the waste resulting from this testing were processed by dewatering and solidification, respectively. TCLP tests were performed on the actual processed waste, and based on the TCLP results, pre-approval for media waste disposal was obtained. (author)