The environmental pollution material which assumed NO produced by a cultured cell an index and a food composition

以培养细胞产生的NO为指标的环境污染物质及食品组合物

• 批准号: 17550146
• 负责人: YOSHITAKE Jun
• 金额: $ 2.44万
• 依托单位: Yamagata Promotional Organization for Industrial Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17550146/
• 关键词: nitrogenmonoxide (NO); endocrine disrupting chemicals (EDCs); macrophages; lipopolysaccharide; estrogen receptor-dependent repressor; 8-ニトログアノシン; シグナル伝達系

Since the endocrine and immune systems share portions of some intracellular signal pathways, endocrine disrupting chemicals (EDCs) are considered potential agents for influencing inflammatory responses. Here, we investigated the effect of EDCs on lipopolysaccharide (LPS)-induced NO production and NF-κB activation in the RAW264.7 mouse macrophage cell line. Five phenol-containing EDCs were investigated, namely bisphenol A (BPA), the alkyl phenols p-n-nonylphenol (NP) and p-n-octylphenol (OP), and the chlorinated phenols 2,4-dichrolophenol (DCP) and pentachlorophenol (PCP). Our results revealed that these chemicals dose-dependently suppressed LPS-induced NO production, as reflected by decreased NOx content. The suppressive effects of BPA, NP and OP, but not PCP or DCP, were blocked by the estrogen receptor (ER) inhibitor, ICI182780. ELISA-based quantification of the DNA-binding activity of free p65 NF-κB showed that LPS-induced NF-κB activation was significantly diminished by EDC treatment. Furthermore, immunocytochemical analysis of 8-nitroguanosine, a unique index of NO-mediated signaling, showed that 8-nitroguanosine formation increased in LPS-stimulated cells, but this increase was inhibited by the tested EDCs. These results demonstrate that EDCs suppress NO production and NF-κB activation in LPS-stimulated macrophages through ER-dependent (BPA, NP, OP) and -independent (PCP, DCP) pathways. The EDCs further inhibited 8-nitroguanosine formation, suggesting that they interfere with NO-mediated signaling. Thus, EDCs might play important roles in the inflammatory response and host defense system against foreign pathogens.

由于内分泌系统和免疫系统共享一些细胞内信号通路，内分泌干扰物（EDCs）被认为是影响炎症反应的潜在因素。本文研究了内分泌干扰物（EDCs）对脂多糖（LPS）诱导的小鼠巨噬细胞株RAW 264. 7产生NO和NF-κB活化的影响。研究了五种含酚类内分泌干扰物，即双酚A（BPA）、烷基酚类对壬基酚（NP）和对辛基酚（OP）、氯代酚类2，4-二氯酚（DCP）和五氯酚（PCP）。我们的研究结果表明，这些化学品的剂量依赖性抑制LPS诱导的NO的产生，反映了减少NOx含量。BPA，NP和OP的抑制作用，而不是PCP或DCP，被雌激素受体（ER）抑制剂ICI 182780阻断。基于ELISA的游离p65 NF-κB DNA结合活性的定量显示，EDC处理显著降低了LPS诱导的NF-κB活化。此外，8-硝基鸟苷的免疫细胞化学分析，NO介导的信号传导的一个独特的指标，表明，8-硝基鸟苷的形成增加，在LPS刺激的细胞，但这种增加被抑制测试的内分泌干扰物。这些结果表明，EDCs通过ER依赖性（BPA，NP，OP）和非依赖性（PCP，DCP）途径抑制LPS刺激的巨噬细胞中NO产生和NF-κB活化。EDCs进一步抑制8-硝基鸟苷的形成，表明它们干扰NO介导的信号传导。因此，内分泌干扰物可能在炎症反应和宿主防御系统中发挥重要作用。

项目成果

Sequential changes of nitric oxide levels in the temporal lobe on applying nitric oxide synthase inhibitors and phenobarbital in kainic acid-treated mice

使用一氧化氮合酶抑制剂和苯巴比妥对红藻氨酸处理的小鼠颞叶一氧化氮水平的连续变化

• 发表时间: 2005
• 期刊: Epilep.Res. 65
• 作者: K. Edamoto;T. Nagayama;K. Ozawa;田中 耕一;J.Yoshitake;J. Yoshitake;K.Uno;N.Ara;K. Uno;N. Ara;K.Asanuma;H.Fujii;H.Morita;N.Kato
• 通讯作者: N.Kato

からだの中のラジカルを電子スピン共鳴(ESR)法で見る-ラジカル画像化の方法と最近の進歩

使用电子自旋共振 (ESR) 观察体内自由基 - 自由基成像方法和最新进展

• 发表时间: 2005
• 期刊: 化学と教育 53
• 作者: K. Edamoto;T. Nagayama;K. Ozawa;田中 耕一;J.Yoshitake;J. Yoshitake;K.Uno;N.Ara;K. Uno;N. Ara;K.Asanuma;H.Fujii;H.Morita;N.Kato;S.Kasai;K.Asanuma;D.Suto;吉村哲彦
• 通讯作者: 吉村哲彦

電子スピン共鳴(ESR, EPR)「生命元素の事典」(桜井弘編)

电子自旋共振（ESR、EPR）《生命元素百科全书》（樱井浩主编）

• 发表时间: 2006
• 作者: Moritoshi Yasunaga;Kentaro Ushiyama;Ikuo Yoshihara;Daekwan Seo;Jung H.Kim;吉村哲彦
• 通讯作者: 吉村哲彦

Toll-like receptor(TLR)2 induced through TLR4 signaling initiated by Helico-bacter pylori cooperatively amplifies iNOS induction hl gastric epithelial cells

幽门螺杆菌启动的 TLR4 信号诱导的 Toll 样受体 (TLR)2 协同放大胃上皮细胞中的 iNOS 诱导

• 发表时间: 2007
• 期刊: Am. J. Physiol. Gastrointest. Liver Physiol. 293
• 作者: K. Edamoto;T. Nagayama;K. Ozawa;田中 耕一;J.Yoshitake;J. Yoshitake;K.Uno;N.Ara;K. Uno
• 通讯作者: K. Uno

LPS誘導NO産生および8-ニトログアノシン形成におけるフェノール含有内分泌かく乱物質の影響

含酚内分泌干扰物对 LPS 诱导的 NO 产生和 8-硝基鸟苷形成的影响

• 发表时间: 2007
• 作者: K. Edamoto;T. Nagayama;K. Ozawa;田中 耕一;J.Yoshitake;J. Yoshitake;K.Uno;N.Ara;K. Uno;N. Ara;K.Asanuma;H.Fujii;H.Morita;N.Kato;S.Kasai;K.Asanuma;D.Suto;吉村哲彦;吉武淳
• 通讯作者: 吉武淳