• Title/Summary/Keyword: inducible NO synthase (iNOS)

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Pathological Lesions and Inducible Nitric Oxide Synthase Expressions in the Liver of Mice Experimentally Infected with Clonorchis sinensis

  • Yang, Qing-Li;Shen, Ji-Qing;Xue, Yan;Cheng, Xiao-Bing;Jiang, Zhi-Hua;Yang, Yi-Chao;Chen, Ying-Dan;Zhou, Xiao-Nong
    • Parasites, Hosts and Diseases
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    • v.53 no.6
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    • pp.777-783
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    • 2015
  • The nitric oxide (NO) formation and intrinsic nitrosation may be involved in the possible mechanisms of liver fluke-associated carcinogenesis. We still do not know much about the responses of inducible NO synthase (iNOS) induced by Clonorchis sinensis infection. This study was conducted to explore the pathological lesions and iNOS expressions in the liver of mice with different infection intensity levels of C. sinensis. Extensive periductal inflammatory cell infiltration, bile duct hyperplasia, and fibrosis were commonly observed during the infection. The different pathological responses in liver tissues strongly correlated with the infection intensity of C. sinensis. Massive acute spotty necrosis occurred in the liver parenchyma after a severe infection. The iNOS activity in liver tissues increased, and iNOS-expressing cells with morphological differences were observed after a moderate or severe infection. The iNOS-expressing cells in liver tissues had multiple origins.

Two acyl phenol glucosides as Inhibitors of iNOS from Popolus davidiana in LPS- activated macrophages

  • Kim, Ji-Sun;Lee, Hwa-Jin;Kim, Yong-Kyun;Ryu, Jae-Ha
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.203.2-204
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    • 2003
  • Nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase (iNOS) is known to be responsible for the vasodilation and hypotension observed in septic shock and inflammation. Inhibitors of iNOS, thus, may be useful candidate for the treatment of inflammatory diseases accompanied by the overproduction of NO. We prepared alcoholic extracts of woody plants and screened the inhibitory activity of NO production in lipopolysaccharide (LPS)-activated macrophages after the treatment of these extracts. (omitted)

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The Effects of Diesel Exhaust Particles on the Alveolar Macrophages for Inducible Nitric Oxide Synthase Induction and Nitric Oxide with Nitrotyrosilated-protein Formation (디젤분진이 폐포대식세포에서 nitric oxide의 생성과 inducible nitric oxide synthase의 발현 및 nitrotyrosilated-protein의 형성에 미치는 효과)

  • Lim Young;Choe Myung-Ok;Lee Kweon-Haeng;Kim Kyung-A;Kim Kil-Soo;Lee Myoung-Heon;Li Tian-Zhu;Lee Soo-Jin;Choe Nong-Hoon
    • Journal of Life Science
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    • v.16 no.2 s.75
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    • pp.192-198
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    • 2006
  • Epidemiological studies have demonstrated an association between exposure to diesel exhaust particles (DEP) and adverse cardiopulmonary effects. Despite the epidemiological proof, the pathogenesis of DEP-related pulmonary diseases remain poorly understood. So, comprehensive in vivo and in vitro researches are required to know the effects of DEP on diverse lung diseases. Alveolar macrophages (AM) and airway epithelial cells are known as important cellular targets in DEP-induced lung diseases. Other studies have shown that nitric oxide (NO) is involved in particle matter induced lung injury. The present study was undertaken to determine whether DEP has an synergistic effects on lipopolysaccharide (LPS)-induced NO formation and inducible nitric oxide synthase (iNOS) with nitrotyrosilated-protein formation in cultured primary alveolar macrophages. The formation of NO was determined through the Griess reaction in the cultured medium and iNOS with nitrotyrosilated-proteins are analyzed by immunohistochemical staining and Western analysis. The results indicate that DEP exposure does not induce NO formation by itself, however DEP showed significant synergistic effects on LPS-induced NO formation. So, our results suggest that DEP inhalation could aggravate inflammatory lung disease through NO formation.

Downregulation of inducible nitric oxide synthase expression by a ceramide analogue in RAW 264.7 murine macrophages

  • Park, Sung-Sik;Chulbu Yim;Kim, Mie-Young;Chun, Young-Jin
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.05a
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    • pp.50-50
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    • 2003
  • Nitric oxide (NO) has been studied and found to be an important intracellular modulator. The excess NO produced by the inducible nitric-oxide synthase (iNOS) is implicated in various inflammatory diseases and cellular injury. Inflammatory cytokines such as TNF- or IL-6 increase intracellular ceramide and ceramide may induce NO production and inflammation. (omitted)

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Taurine Activates ERK2 and Induces the Production of Nitric Oxide in Osteoblast-like UMR-106 Cells

  • Park, Sung-Youn;Kim, Harriet;Kim, Sung-Jin
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.145-145
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    • 1998
  • In the present study, we have demonstrated that taurine could stimulate the production of nitric oxide and the activity of ERK2 (extracellular signal regulated protein kinase or pp42 MAP kinase). Nitric oxide(NO), the product of inducible nitric oxide synthase(iNOS), is known to be implicated in the metabolism of bone. ERK cascade plays a key role in the gene expression of iNOS in osteoblastic cell. We investigated whether taurine (l-20mM) could stimulate ERK2 activity, nitric oxide production, and inducible nitric oxide synthase in osteoblast-like UMR-106 cells. Nitric oxide was measured spectophotometrically as nitrite and the activation of ERK2 and iNOS was studied using Western 145 blot analysis. Taurine increased the production of nitric oxide in a dose-dependent manner and the effect was reached to a maximum at 10 mM. The activation of iNOS were consistent with NO levels. The tyrosine phosphorylation of ERK2 was increased by taurine in a time-dependent manner. The these result suggest that taurine might stimulate the production of nitric oxide in osteoblast-like cells by the activation of ERK2 and could regulate the metabolism of bone via nitric oxide.

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Down-regulation of inducible nitric oxide synthase and tumor necrosis factor-a expression by Bisphenol A via nuclear factor-kB inactivation in macrophages

  • Kim, Ji-Young;Jeong, Hye-Gwang
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.293.2-293.2
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    • 2002
  • Bisphenol A [BPA. 2.2-bis(4-hydroxyphenyl)propane] is reported to have estrogenic activity: however. its influence on cytokine production or immune system function remains unclear. In this study. we investigated the effects of BPA on the production of nitric oxide (NO) and tumor necrosis factor-a (TNF-a), and on the level of inducible nitric oxide synthase (iNOS) and TNF-a gene expression in mouse macrophages. BPA alone did not affect NO or TNF-a production. (omitted)

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Inhibition of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Activity by $1,2,3,4,6-Penta-Ο-galloyl-{\beta}-D-glucose$ in Murine Macrophage Cells

  • Lee, Sung-Jin;Lee, Ik-Soo;Mar, Woong-Chon
    • Archives of Pharmacal Research
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    • v.26 no.10
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    • pp.832-839
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    • 2003
  • Activated macrophages express inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), and produce excessive amounts of nitric oxide (NO) and prostaglandin E$_2$ (PGE$_2$), which play key roles in the processes of inflammation and carcinogenesis. The root of Paeonia lactiflora Pall., and the root cortex of Paeonia suffruticosa Andr., are important Chinese crude drugs used in many traditional prescriptions. 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) is a major bioactive constituent of both crude drugs. PGG has been shown to possess potent anti-oxidant, anti-mutagenic, anti-proliferative and anti-invasive effects. In this study, we examined the inhibitory effects of 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) isolated from the root of Paeonia lactiflora Pall. on the COX-2 and iNOS activity in LPS-activated Raw 264.7 cells, COX-1 in HEL cells. To investigate the structure-activity relationships of gallate and gallic acid for the inhibition of iNOS and COX-2 activity, we also examined (-)-epigallocatechin gallate (EGCG), gallic acid, and gallacetophenone. The results of the present study indicated that PGG, EGCG, and gallacetophenone treatment except gallic acid significantly inhibited LPS-induced NO production in LPS-activated macrophages. All of the four compounds significantly inhibited COX-2 activity in LPS-activated macrophages. Among the four compounds examined, PGG revealed the most potent in both iNOS ($IC_{50}$ = 18 $\mu\textrm{g}/mL$) and COX-2 inhibitory activity (PGE$_2$: $IC_{50}$ = 8 $\mu\textrm{g}/mL$ and PGD$_2$: $IC_{50}$ = 12 $\mu\textrm{g}/mL$), respectively. Although further studies are needed to elucidate the molecular mechanisms and structure-activity relationship by which PGG exerts its inhibitory actions, our results suggest that PGG might be a candidate for developing anti-inflammatory and cancer chemopreventive agents.

Suppressive Effects of Chrysanthemum zawadskii var. latilobum Flower Extracts on Nitric Oxide Production and Inducible Nitric Oxide Synthase Expression (구절초 꽃 추출물의 Nitric Oxide 생성과 Inducible Nitric Oxide Synthase 발현 억제 효과)

  • Han, Ji-Young;Kim, Young-Hwa;Sung, Jee-Hye;Um, Yu-Rry;Lee, Yi;Lee, Jun-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.12
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    • pp.1685-1690
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    • 2009
  • In this study, we investigated the effect of C. zawadskii extract on nitric oxide (NO) production, prostaglandin E2 (PGE2) production, protein and mRNA expression of inducible nitric oxide synthase (iNOS) in LPS-induced RAW 264.7 macrophage cells. C. zawadskii extract (5~50 μg/mL) significantly inhibited LPS-induced NO production in a concentration-dependent manner ranging from 23.3% to 100%. Consistent with the inhibitory effect on NO production, C. zawadskii extract inhibited the protein expression and mRNA expression of iNOS. Although flower extracts of C. zawadskii was not effective on the expression of PGE2 and COX-2, flower extracts of C. zawadskii, however, showed a strong anti-inflammatory activity through inhibition of NO production and iNOS expression. The present results suggest that C. zawadskii extract has an inhibitory effect on NO production, and thus can be used as an anti-inflammatory agent.

Suppressive effects on the expression of cyclooxygenase-2 and inducible nitric oxide synthase by a natural sesquiterpenoid in lipopolysaccharide-stimulated mouse macrophage cells

  • Min, Hye-Young;Park, Hyen-Joo;Park, Eun-Jung;Lee, Sang-Kook
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.101-101
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    • 2003
  • Prostaglandins (PGs) and nitric oxide (NO) produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the process of inflammation and carcinogenesis. On this line, the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents. In our continuing efforts of searching for novel cancer chemopreventive agents from natural products, we isolated natural sesquiterpenoids as potential COX-2 and iNOS inhibitors in cultured lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells. Alantolactone, a natural eudesmane-type sesquiterpenoid, exhibited a potent inhibition of COX-2 (IC50 = 0.4 $\mu\textrm{g}$/$m\ell$) and iNOS activity (IC50 = 0.08 $\mu\textrm{g}$/$m\ell$) in the assay system determined by PGE2 and NO accumulation, respectively. The inhibitory potential of alantolactone on the PGE2 and NO production was well coincided with the suppression of COX-2 and iNOS protein and mRNA expression in LPS-induced macrophages. Furthermore, alantolactone inhibited NF-kB but not AP-l binding activity on nuclear extracts evoked by LPS-stimulated macrophage cells, suggesting the possible involvement of NF-kB in the regulation of COX-2 and iNOS expression. In further study with COX-2-expressing human colon HT-29 cells, alantolactone inhibited the cell proliferation, down-regulated COX-2, and inhibited the ERK phosphorylation in the early time. These results suggest that a natural sesquiterpenoid alantolactone might be a potential lead candidate for further developing COX-2 or iNOS inhibitor possessing cancer chemopreventive or anti-inflammatory activity

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Inhibition of Inducible Nitric Oxide Synthase by Agaricus bisporus Extract in RAW 264.7 Macrophages

  • Ahn, Ji-Yun;Lee, Hyun-Jung;Moon, Mi-Kyung;Kim, Su-Na;Ha, Tae-Youl
    • Preventive Nutrition and Food Science
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    • v.13 no.4
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    • pp.362-365
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    • 2008
  • Agaricus bisporus, also known as white button mushroom, is one of the most popular mushrooms consumed in Korea. This mushroom contains high concentrations of flavanoids and exhibits antioxidant activity. In this study, we examined the effects of Agaricus bisporus ethanol extract (ABE) on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells. Nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) protein levels were assessed in cells treated with $100\;{\mu}M$ LPS in the presence or absence of ABE. 0.5 mg/mL of ABE suppressed NO production significantly. Moreover, ABE inhibited levels of iNOS protein. Taken together, these results suggest that ABE exerts anti-inflammatory activity in LPS-induced inflammation in RAW 264.7 cells.