Mechanism on Enhancing effect of chlorinated organic solvents as groundwater pollutants on Type I Allergy

地下水污染物氯化有机溶剂对I型过敏的增强作用机制

基本信息

  • 批准号:
    15590111
  • 负责人:
  • 金额:
    $ 2.18万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2003
  • 资助国家:
    日本
  • 起止时间:
    2003 至 2004
  • 项目状态:
    已结题

项目摘要

The prevalence rate of allergic diseases such as bronchial asthma and rhinitis is increasing in industrial areas and countries. There are some reports on epidemiological studies that may suggest a link between the incidence of allergic disease and environmental pollutants, such as diesel exhaust particles (DEPs), formaldehyde and volatile organic compounds (VOC). Chlorinated organic solvents are classified into VOC, and recently have become major environmental pollutants. Previously we observed the enhancing effects of some chlorinated organic solvents, such as tetrachloroethylene (PCE) and trichloroethylene (TCE), on histamine release from rat mast cells in vitro. In the present study, we investigated the enhancing effect of low concentration of PCE and TC dissolved in drinking water on Wistar rat. The chlorinated organic solvents enhanced passive cutaneous anaphylaxis (PCA) in a dose-dependent manner. Rat mast cell RBL-2H3 were incubated with anti-dinitrophenol (DNP) monoclonal IgE antibody, and then stimulated by DNP-BSA in the presence of PCE (0.01, 0.1 and 1 mg/L) or TCE (0.03, 0.3 and 3 mg/L). The conditioned medium and cell lysate were collected, and measured IL-4, TNF-α and MCP-1 by ELISA. Each inflammatory mediator production was increased in a dose-dependent manner. Furthermore, mRNA expression of them was evaluated by semi-quantitative RT-PCR, these mRNA expressions were found to be up-regulated by the exposure of PCE and TCE. Thus, this overexpression of inflammatory mediator from RBL-2H3 exposed to PCE and TCE is associated with inflammatory response in late phase. These results suggest that PCE and TCE, even in a low concentration, may affect the immune response via the modulation of cytokine production in mast cells, and lead to the augmentation of allergic diseases.
过敏性疾病如支气管哮喘和鼻炎的患病率在工业地区和国家中正在增加。有一些流行病学研究报告可能表明过敏性疾病的发病率与环境污染物之间存在联系,如柴油机排气颗粒(DEP),甲醛和挥发性有机化合物(VOC)。氯代有机溶剂属于VOC,近年来已成为主要的环境污染物。我们观察了四氯乙烯(PCE)和三氯乙烯(TCE)等氯化有机溶剂对肥大细胞释放组胺的促进作用。本实验研究了低浓度的PCE和TC对Wistar大鼠的增敏作用。氯化有机溶剂以剂量依赖性方式增强被动皮肤过敏反应(PCA)。将大鼠肥大细胞RBL-2 H3与抗二硝基酚(DNP)IgE单克隆抗体孵育,然后在PCE(0.01、0.1和1 mg/L)或TCE(0.03、0.3和3 mg/L)存在下,用DNP-BSA刺激。收集条件培养液和细胞裂解液,用ELISA法测定IL-4、TNF-α和MCP-1。每种炎症介质的产生以剂量依赖性方式增加。用半定量RT-PCR方法检测其mRNA的表达,发现PCE和TCE均能上调其mRNA的表达。因此,这种来自暴露于PCE和TCE的RBL-2 H3的炎症介质的过表达与晚期的炎症反应相关。这些结果表明,PCE和TCE,即使在低浓度下,也可能通过调节肥大细胞中细胞因子的产生来影响免疫应答,并导致过敏性疾病的加重。

项目成果

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