• Title/Summary/Keyword: Inducible NO synthase

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Ceramide analogs inhibit inducible nitric oxide synthase expression and nitric oxide production in interferon-gamma and lipopolysaccharide-stimulated RAW 264.7 macrophages.

  • Park, Sung-Sik;Kim, Hae-Jong;Yim , Chul-Bu;Kim, Mie-Young;Chun, Young-Jin
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.313.1-313.1
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    • 2002
  • Nitric oxide (NO) production through the inducible nitric-oxide synthase (iNOS) pathway has been implicated in inflammatory diseases and cellular injury. Inhibition of various genes related to inflammation, including iNOS is one of the major roles of well-known anti-inflammatory drugs. In the present study, the effects of ceramide analogs on iNOS expression and NO production were evaluated to investigate how ceramide and its structurally related analogs modulate NO-mecliated cellular signals and inflammation. (omitted)

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YH439, a Hepatoprotective Agent, Suppresses Cytokines and Nitric Oxide Production in LPS-primed Rats Administered with $CCL_4$ ($CCI_4$와 Lipopolysaccharide로 유도한 흰쥐 간 독성에 대한 YH439의 방어작용 : cytokines 및 nitric oxide 생성의 억제)

  • 김연숙;이종욱;김낙두
    • YAKHAK HOEJI
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    • v.43 no.2
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    • pp.198-207
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    • 1999
  • The aim of the present investigation was to examine whether YH439, a hepatoprotective agent, exerts protective effect against hepatotoxicity and reduces the production of cytokines and NO in lipopolysaccharide (LPS)-primed rats with carbon tetrachloride ($CCl_4$). Administration of LPS following a single dose of CCl4 injection resulted in remarkable elevations of the serum $TNF{\alpha},{\;}IL-l{\beta$ and IL-6 level. The serum NO level was moderately elevated and severe liver damage was evidenced by increases in serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities. YH439 decreased the levels of TNF, $IL-l{\beta}$, IL-6, ALT, SDH as well as NO in the serum elevated by CCl4+LPS in a dose-dependent manner. Inducible nitric oxide synthase (iNOS) level was decreased in the liver of rats treated with YH439. The increased iNOS activity induced by LPS and $interferon-{\gamma}$ was significantly decreased in RAW 264.7 cells by YH439 treatment. YH439 increased the GSH level decreased by $CCl_4+LPS$ and suppressed the ratio of GSSG/GSH. The reduction of hepatotoxicity by YH439 may associated with the decrease in the production of cytokines as well as suppression of iNOS protein in conjunction with an increase in the GSH level.

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INHIBITION OF INDUCIBLE NITRIC OXIDE SYNTHASE EXPRESSION BY SILYMARIN IN LPS-STIMULATED MACROPHAGES

  • Kang, Jong-Soon;Jeon, Young-Jin;Yang, Kyu-Hwan;Kim, Hwan-Mook
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.130-130
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    • 2001
  • Silymarin, a polyphenolic flavonoid antiodant, has been shown to have anti-inflammatory, hepatoprotective, and anticarcinogenic effects. In the present study, we report the inhibitory effect of silymarin on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) mRNA expression in macrophages. In vivo administration of silymarin attenuated NO production of peritoneal macrophages in lipopolysaccharide (LPS)-treated mice.(omitted)

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Human placental extract suppresses lipopolysaccharide-induced expressions of cyclooxygenase-2 and inducible nitric oxide synthase in mouse BV2 microglial cells

  • Yang, Sang-Eun;Kim, Yong-Suk;Park, Dong-Suk
    • Journal of Acupuncture Research
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    • v.22 no.2
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    • pp.111-121
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    • 2005
  • Human placental extract (HPE), which is prepared from the placenta of healthy pregnant females, has been widely used in clinical field. HPE is known to possess anti-inflammatory, anti-viral, anti-oxidative, anti-mutagenic, and analgesic properties. In this study, the effect of HPE against lipopolysaccharide (LPS)-induced inflammation was investigated. From the present results, HPE was shown to suppress prostaglandin E2 synthesis (PGE2) and nitric oxide (NO) production by inhibition on the LPS-stimulated enhancement of the cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions in mouse BV2 microglial cells. These results suggest that HPE may offer a valuable mean of therapy for the treatment of brain inflammatory diseases by attenuating LPS-induced PGE2 and NO production.

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Nelumbinis Folium Methanol Extract Regulates Inducible Nitric Oxide Synthase Signaling Pathways in Mouse Peritoneal Macrophages (하엽(荷葉) 메탄올 추출물의 마우스 대식세포 inducible nitric oxide synthase 합성과 신호전달에 대한 조절)

  • Lee, Si-Eun;Lee, Mi-Hwa;Choi, Ho-Young;Sohn, Nak-Won;Kang, Hee
    • The Korea Journal of Herbology
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    • v.27 no.1
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    • pp.65-71
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    • 2012
  • Objective : Nelumbinis Folium (NF) is used for diarrhea, headache and dizziness in traditional medicine. In this paper, we examined the anti-inflammatory effects of the methanol extract of NF in mouse macrophages. Methods : Peritoneal macrophages from thioglycollate medium-injected mice were cultured and stimulated with lipopolysaccharide(LPS) or LPS/interferon(IFN)-${\gamma}$ for viability assay, cytokine measurement and Western blotting. Results : NF methanol extract suppressed the levels of nitric oxide (NO) through reduction of inducible NO synthase in a concentration-dependent manner. The extract reduced LPS/IFN-${\gamma}$-stimulated STAT1 phosphorylation and LPS-induced $I{\kappa}B{\alpha}$ degradation through inhibition of $I{\kappa}B{\alpha}$ kinase activation. The extract also inhibited p38, JNK/SAPK and ERK1/2 activation. Conclusions : Our findings suggested that NF has anti-inflammatory activity, and have a potential for therapeutic application. Further research is required to investigate its anti-inflammatory active compounds.

Effect of aging on expression of nitric oxide and inducible nitric oxide synthase in human gingival fibroblasts (노화가 사람 치은섬유아세포의 nitric oxide와 inducible nitric oxide synthase 발현에 끼치는 영향)

  • Ji, Suk;Kook, Jung-Ki;Park, Joo-Cheol;Kim, Heung-Joong;Jang, Hyun-Seon;Kim, Chong-Kwan;Kim, Byung-Ock
    • Journal of Periodontal and Implant Science
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    • v.36 no.2
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    • pp.361-373
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    • 2006
  • 치주질환의 진행이 나이에 의해 영향을 받는다는 사실은 알려져 있으나 노화에 따른 치주조직 세포의 기능적인 변화에 관한 사실은 많이 알려져 있지 않다. 노화에 따른 세포의 노화가 치주질환의 진행에 어떠한 여향을 끼치는가를 아는 것은 중요하다. 염증 상태에서 nitric oxide (NO)는 조직 파괴에 관여하는 인자로 작용하여 치주질환의 진행에 관여하는 것으로 알려져 있다. 따라서 이 연구는 사람의 치은에서 배양된 치은섬유아세포를 이용하여 세포의 노화에 따른 NO와 이의 합성효소인 inducible nitric oxide synthase (iNOS)의 발현을 알아봄으로써 세포의 노화가 치주질환의 진행에 끼치는 영향에 대해 알아보고자 하였다. 10세의 환자와 55세의 환자에서 각각 채취한 치은에서 배양된 세포와 10세의 환자에서 채취한 세포를 계속적인 계대배양을 통해 얻은 실험실 상 노화된 세포를 포함하여 총 3 종류의 치은섬유세포를 실험에 이용하였다. Hot phenol-water extraction을 통해 추출된 Porphyromonas, gingivalis ATCC 33277 lipopolysaccharide (LPS)와 재조합 $IFN-{\gamma}$ 를 세포에 적용시켜 Griess assay를 통해 조건화된 배지에서 NO를 측정하였다. 20세와 55세의 환자에서 채취된 치은 조직과 총 3 종류의 배양된 세포에 NOS-II 항체를 적용시켜 iNOS 단백질 발현을 관찰하였다. Total RNA를 추출하여 RT-PCR를 통해 iNOS mRNA의 발현을 분석하였다. 치은섬유아세포에서 NO는 자발적으로 발생되었고, 이러한 발현은 젊은 세포보다 노화된 세포에서 강하였다. P, gingivalis LPS와 제조합 $IFN-{\gamma}$는 치은섬유아세포에서 NO의 발현을 증가시켰고, 이러한 발현은 젊은 세포보다 노화된 세포에서 강하였다. 면역조직화학 염색에서 iNOS 단백질은 젊은 사람과 노화된 사람의 치은 조직 모두에서 치은섬유아세포와 상피의 기저층 세포와 염증세포에서 발현되었으나 노화에 따른 발현의 차이를 구별할 수는 없었다. 세포의 면역염색에서 iNOS 단백질은 노화된 세포에서 강하게 발현되었고 이러한 발현은 LPS와 $IFN-{\gamma}$ 에 의해 강화되었다. LPS와 $INF-{\gamma}$ 의 조건이 주어지지 않은 상태에서 iNOS mRNA는 젊은 세포에서보다 노화된 세포에서 강하게 발현되었다. 이러한 결과를 통해 세포의 노화가 NO와 iNOS 발현을 증가시킴으로서 치주질환의 진행에 영향을 끼칠 수 있음을 시사하였다.

Ovalbumin Induces Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Expression (Ovalbumin에 의한 cyclooxygenase-2와 inducible nitric oxide synthase 유도)

  • Lee, A-Neum;Park, Se-Jeong;Jeong, Ae-Ri;Lee, Jae-Ran;Park, Hye-Jeong;Kim, Soo-Jung;Min, In-Soon;Youn, Hyung-Sun
    • Korean Journal of Food Science and Technology
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    • v.43 no.1
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    • pp.110-113
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    • 2011
  • Egg allergies are the most prevalent food hypersensitivity in children. The major egg allergens are proteins, such as ovalbumin (OVA) and ovomucoid (OVM), which are mainly contained in egg whites. OVA is the major protein in egg white, comprising 54% of the total protein content. OVA has been widely used in experimental inhalant and dietary allergy animal models, but its mechanism has not been clearly identified. In this study, we showed that OVA induced nuclear factor-${\kappa}B$ activation. OVA also induced the expression of cyclooxygenase-2 and inducible nitric oxide synthase. These data suggest new approaches for developing efficient anti-allergic strategies.

Nitric oxide production and inducible nitric oxide synthase expression induced by Porphyromonas gingivalis lipopolysaccharide (Porphyromonas gingivalis의 세균내독소가 RAW264.7세포에서의 nitric oxide의 생성과 inducible nitric oxide synthase의 발현에 미치는 영향 및 기전)

  • Paek, Eun-Young;Choi, Eun-Young;Choi, Jeom-II;Lee, Ju-Yun;Kim, Sung-Jo
    • Journal of Periodontal and Implant Science
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    • v.35 no.4
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    • pp.1081-1095
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    • 2005
  • 본 연구는 치주질환 주요 병인균주 중의 하나인 Porphyromonas gingivalis의 세균내독소가 마우스 대식 세포주인 RAW264.7 세포에서의 nitric oxide의 생성과 iNOS의 발현에 미치는 영향을 분석하고 그 기전을 규명하기 위해 수행되었다. Butanol추출법과 phenol-water법에 의해 P. gingivalis 381로부터 세균내독소를 추출하였으며, NO의 생성은 배양 상층액 내의 nitrite 농도를 측정하여 결정하였다. 또한, iNOS의 western blot 분석과 reverse transcription (RT)-PCR 산물의 분석을 수행하였다. P. gingivalis의 세균내독소는 부가적인 자극이 없는 상태에서도 iNOS의 발현과 NO 생성을 유발하였으며, NF- ${\kappa}B$, microtubule polymerization, protein tyrosine kinase, 그리고 protein kinase C 등이 P. gingivalis 세균내독소에 의한 NO 생성에 간여하는 것으로 여겨진다. 또한, P. gingivalis 세균내독소에 의한 NO 생성에는 L-arginine이 요구되었다. P. gingivalis 세균내독소에 의한 NO 생성은 염증성 치주질환의 발병과 진행에 있어 중요한 역할을 하는 것으로 여겨진다.

Elevation of Nitric Oxide Synthase Activity by Dimethyladenosine from Silkworm Pupae in Aged Rats

  • Ahn, Mi-Young;Han, Jea-Woong;Hong, Yoo-Na;Hwang, Jae-Sam
    • Toxicological Research
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    • v.24 no.3
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    • pp.169-174
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    • 2008
  • This study examined the mechanisms underlying the effects of the vasorelaxation active substance(VAS), dimethyladenosine-5'-L-arabinose, and its partial purification fraction on nitric oxide synthase in improving erectile dysfunction with particular focus on the nitric oxide (NO)-cGMP pathways. Two rat models, 9-month-old SD rats and 11-month-old SD rats, were given VAS(40 mg/kg per day) for 4 days, The aqueous fraction of silworm male pupae extract; semi-purified VAS(100 mg/kg per day) for 10 days, respectively. The NOS activities of the following three enzymes were examined: neuronal NO synthase(nNOS), inducible NOS(iNOS), endothelial NOS(eNOS), vascular endothelial growth factor on endothelial cells(VEGF) and anti-inflammation effect of Tumor necrosis factor-$\alpha$. The results showed increases in the nitric oxide synthase activities. Western blotting of the tissue homogenate showed an increase in the nNOS level in the brain and tongue, and an increase in the endothelial NO synthase(eNOS) level in penis. However, there was little association with VEGF production in HUVEC endothelial cells and no relationship with TNF-$\alpha$ which showed low levels.

Ursolic Acid Reduces Mycobacterium tuberculosis-Induced Nitric Oxide Release in Human Alveolar A549 cells

  • Zerin, Tamanna;Lee, Minjung;Jang, Woong Sik;Nam, Kung-Woo;Song, Ho-yeon
    • Molecules and Cells
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    • v.38 no.7
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    • pp.610-615
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    • 2015
  • Alveolar epithelial cells have been functionally implicated in Mycobacterium tuberculosis infection. This study investigated the role of ursolic acid (UA)-a triterpenoid carboxylic acid with potent antioxidant, anti-tumor, anti-inflammatory, and anti-tuberculosis properties in mycobacterial infection of alveolar epithelial A549 cells. We observed that M. tuberculosis successfully entered A549 cells. Cytotoxicity was mediated by nitric oxide (NO). A549 toxicity peaked along with NO generation 72 h after infection. The NO generated by mycobacterial infection in A549 cells was insufficient to kill mycobacteria, as made evident by the mycobacteria growth indicator tube time to detect (MGIT TTD) and viable cell count assays. Treatment of mycobacteria-infected cells with UA reduced the expression of inducible nitric oxide synthase, NO generation, and eventually improved cell viability. Moreover, UA was found to quench the translocation of the transcription factor, nuclear factor kappa B (NF-${\kappa}B$), from the cytosol to the nucleus in mycobacteria-infected cells. This study is the first to demonstrate the cytotoxic role of NO in the eradication of mycobacteria and the role of UA in reducing this cytotoxicity in A549 cells.