The In Vitro Proinflammatory Properties of Water Accommodated Sediment Extracts from a Creosote-Contaminated US Environmental Protection Agency Superfund Site.

The In Vitro Proinflammatory Properties of Water Accommodated Sediment Extracts from a Creosote-Contaminated US Environmental Protection Agency Superfund Site.
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美国环境保护局超级基金场地杂酚油污染的水处理沉积物提取物的体外促炎特性。

DOI:
10.1002/etc.5001
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发表时间:
2021-06
影响因子:
4.1
通讯作者:
Rice CD
Rice CD
中科院分区:
环境科学与生态学3区
文献类型:
--
作者:
Silva RA;Di Giulio RT;Rice CD

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美国弗吉尼亚州朴茨茅斯附近的伊丽莎白河南部分支是北美杂酚油污染最严重的次河口之一,也是大西洋木材工业(AW)EPA超级基金站点的前位置。我们以前证明,成年AW鱼原位收集有严重的肝脏病变,包括肝母细胞瘤和肝细胞癌,以及抑制循环抗体反应相比,历史参考网站。此外,AW鱼的几种先天免疫功能较高,包括肝环氧合酶-2(考克斯-2)的表达升高,表明促炎环境。为了进一步研究AW污染物调节先天免疫功能的潜力,本研究使用RAW264.7小鼠巨噬细胞作为体外模型来开发快速筛选的新方法学(NAM)。脂多糖(LPS)刺激的一氧化氮分泌的巨噬细胞是一个快速,灵敏,预测的体外系统筛选潜在的免疫毒性污染物作为单一的化合物或复杂的混合物。与参考部位相比,过滤灭菌的AW沉积物提取物(水调节组分)诱导一氧化氮和IL-6分泌以及诱导型一氧化氮合酶(iNOS)和考克斯-2蛋白的水平与单独LPS处理诱导的水平相当或更高。提取物还增加了巨噬细胞的吞噬活性。使用鲎试剂测定,我们表明AW提取物中的细菌内毒素水平高于参考提取物,多粘菌素B螯合改善了促炎作用。这些研究结果阐明了现实的沉积物成分以外的有毒化合物,以前与发育异常和致癌作用的?从AW网站。也许这些数据还表明,与污染较轻的地点相比,在世界各地许多污染严重的地点存在适应污染物的沉积物微生物财团。
The Southern branch of the Elizabeth River near Portsmouth Virginia, USA, is one of the most creosote-polluted sub-estuaries in North America and former location of the Atlantic Wood Industries (AW) EPA superfund site. We previously demonstrated that adult AW killifish collected in situ had severe hepatic lesions, including hepatoblastoma and hepatocellular carcinoma, as well as suppressed circulating antibody responses compared to a historical reference site. Moreover, several innate immune functions were higher in AW fish, including elevated expression of hepatic cyclo-oxygenase-2 (COX-2), suggesting a pro-inflammatory environment. To further examine the potential of AW contaminants to modulate innate immune function(s) this study used RAW264.7 mouse macrophages as an in vitro model to develop new approach methodologies (NAM) for rapid screening. Lipopolysaccharide (LPS)-stimulated nitric oxide secretion by macrophages is a rapid, sensitive, and predictive in vitro system for screening potentially immunotoxic contaminants as single compounds or as complex mixtures. Compared to the reference site, filter-sterilized AW sediment extracts (water accommodated fractions) induced nitric oxide and IL-6 secretion as well as inducible-nitric oxide synthase (iNOS) and COX-2 proteins at levels comparable to, or higher than induced by LPS treatments alone. Extracts also increased phagocytic activity by macrophages. Using a limulus lysate assay, we show that bacterial endotoxin levels in AW extracts are higher than in reference extracts and polymyxin-B chelation ameliorates pro-inflammatory effects. These findings illuminate the reality of sediment constituents other than toxic compounds previously associated with developmental abnormalities and carcinogenesis in killifish from the AW site. Perhaps these data also suggest the presence of contaminant-adapted consortia of sediment microbes at many heavily polluted sites worldwide compared to less contaminated sites.
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