Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Clinical Cooperation Group Inflammatory Lung Diseases, Institute of Lung Biology and Disease and Asklepios Fachkliniken Muenchen-Gauting, Robert-Koch-Allee 29, 82131 Gauting, Germany.
Part Fibre Toxicol. 2009 Oct 16;6:27. doi: 10.1186/1743-8977-6-27.
Cytochrome P450 monoxygenases play an important role in the defence against inhaled toxic compounds and in metabolizing a wide range of xenobiotics and environmental contaminants. In ambient aerosol the ultrafine particle fraction which penetrates deeply into the lungs is considered to be a major factor for adverse health effects. The cells mainly affected by inhaled particles are lung epithelial cells and cells of the monocyte/macrophage lineage.
In this study we have analyzed the effect of a mixture of fine TiO2 and ultrafine carbon black Printex 90 particles (P90) on the expression of cytochrome P450 1B1 (CYP1B1) in human monocytes, macrophages, bronchial epithelial cells and epithelial cell lines. CYP1B1 expression is strongly down-regulated by P90 in monocytes with a maximum after P90 treatment for 3 h while fine and ultrafine TiO2 had no effect. CYP1B1 was down-regulated up to 130-fold and in addition CYP1A1 mRNA was decreased 13-fold. In vitro generated monocyte-derived macrophages (MDM), epithelial cell lines, and primary bronchial epithelial cells also showed reduced CYP1B1 mRNA levels. Benzo[a]pyrene (BaP) is inducing CYB1B1 but ultrafine P90 can still down-regulate gene expression at 0.1 muM of BaP. The P90-induced reduction of CYP1B1 was also demonstrated at the protein level using Western blot analysis.
These data suggest that the P90-induced reduction of CYP gene expression may interfere with the activation and/or detoxification capabilities of inhaled toxic compounds.
细胞色素 P450 单加氧酶在防御吸入性有毒化合物以及代谢广泛的外源性化学物质和环境污染物方面发挥着重要作用。在环境气溶胶中，穿透肺部深处的超细颗粒部分被认为是对健康产生不利影响的主要因素。受吸入颗粒主要影响的细胞是肺上皮细胞和单核细胞/巨噬细胞谱系的细胞。
在这项研究中，我们分析了细 TiO2 和超细碳黑 Printex 90 颗粒（P90）混合物对人单核细胞、巨噬细胞、支气管上皮细胞和上皮细胞系中细胞色素 P450 1B1（CYP1B1）表达的影响。P90 可强烈下调单核细胞中的 CYP1B1 表达，最大下调发生在 P90 处理 3 小时后，而细 TiO2 和超细 TiO2 则没有影响。CYP1B1 下调多达 130 倍，此外 CYP1A1 mRNA 减少 13 倍。体外生成的单核细胞衍生的巨噬细胞（MDM）、上皮细胞系和原代支气管上皮细胞也显示 CYP1B1 mRNA 水平降低。苯并[a]芘（BaP）可诱导 CYB1B1，但超细 P90 仍可在 0.1 μM BaP 下下调基因表达。Western blot 分析也证明了 P90 诱导的 CYP1B1 减少。
这些数据表明，P90 诱导的 CYP 基因表达减少可能会干扰吸入性有毒化合物的激活和/或解毒能力。
