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2007 Fiscal Year Final Research Report Summary

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

Research Project

Project/Area Number 17550146
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental chemistry
Research InstitutionYamagata Promotional Organization for Industrial Technology

Principal Investigator

YOSHITAKE Jun  Yamagata Promotional Organization for Industrial Technology, Research and Development Sectionl, Researcher (70414349)

Co-Investigator(Kenkyū-buntansha) SHIGENOBU Kasai  東北工業大学, Tohoku Institute of Technology, Environmental information engineering department, Associate professor (70342730)
TOMOKAZU Matsuei  Tokoku University, Environmental information engineering department, Professor (70173797)
Project Period (FY) 2005 – 2007
Keywordsnitrogenmonoxide (NO) / endocrine disrupting chemicals (EDCs) / macrophages / lipopolysaccharide / estrogen receptor-dependent repressor
Research Abstract

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.

  • Research Products

    (5 results)

All 2008 2007

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (2 results)

  • [Journal Article] Suppression of NO production and 8-nitroguanosine formation by phenol-containing endocrine-disrupting chemicals in LPS-stimulated macrophages : involvement of estrogen receptor-dependent or -independent pathways.2008

    • Author(s)
      J.Yoshitake
    • Journal Title

      Nitric Oxide 18

      Pages: 223-228

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Toll-like receptor(TLR)2 induced through TLR4 signaling initiated by Helico-bacter pylori cooperatively amplifies iNOS induction in gastric epithelial cells.2007

    • Author(s)
      K.Uno
    • Journal Title

      Am.J.Physiol.Gastrointest. Liver Physiol. 293

      Pages: G1004-G1012

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Disruption of gastric barrier function by luminal nitrosative stress : A potential chemical insult to human gastro-oesophageal junction.2007

    • Author(s)
      N.Ara
    • Journal Title

      Gut 57

      Pages: 306-313

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Presentation] フェノール含有内分泌かく乱物質がLPS誘導NO産生経路に及ぼす影響2007

    • Author(s)
      吉武淳
    • Organizer
      第80回日本生化学会大会
    • Place of Presentation
      神奈川県 横浜市
    • Year and Date
      20071211-20071215
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 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2007

    • Author(s)
      吉武淳
    • Organizer
      第29回日本フリーラジカル学会学術集会/日本過酸化脂質・フリーラジカル学会第31回大会合同学会
    • Place of Presentation
      愛知県 名古屋市
    • Year and Date
      20070609-20070610
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2011-06-18  

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