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
| Project/Area Number |
17550146
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental chemistry
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| Research Institution | Yamagata Promotional Organization for Industrial Technology |
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Principal Investigator |
YOSHITAKE Jun Yamagata Promotional Organization for Industrial Technology, Research and Development Sectionl, Researcher (70414349)
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| 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)
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| Project Period (FY) |
2005 – 2007
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| Keywords | nitrogenmonoxide (NO) / endocrine disrupting chemicals (EDCs) / macrophages / lipopolysaccharide / estrogen receptor-dependent repressor |
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| 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.
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