Ultrafine carbon particles down-regulate CYP1B1 expression in human monocytes.
Ultrafine carbon particles down-regulate CYP1B1 expression in human monocytes.
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DOI：
10.1186/1743-8977-6-27
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发表时间：
2009-10-16
影响因子：
10
通讯作者：
Hofer TP
中科院分区：
文献类型：
--
作者：
Eder C;Frankenberger M;Stanzel F;Seidel A;Schramm KW;Ziegler-Heitbrock L;Hofer TP
细胞色素P450单加氧酶在抵抗吸入的有毒化合物和代谢广泛的外源性物质和环境污染物中起重要作用。在环境气溶胶中，深入肺部的超细颗粒部分被认为是不利健康影响的主要因素。主要受吸入颗粒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TiO 2和超细炭黑Printex 90颗粒（P90）的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 1B 1（CYP 1B 1）表达的影响。P90处理3 h后，单核细胞CYP 1B 1的表达显著下调，而细、超细二氧化钛则无明显影响。CYP 1B 1下调高达130倍，此外CYP 1A 1 mRNA降低13倍。体外产生的单核细胞源性巨噬细胞（MDM）、上皮细胞系和原代支气管上皮细胞也显示出CYP 1B 1 mRNA水平降低。苯并[a]芘（BaP）诱导CYB 1B 1，但超细P90在0.1 μM的BaP下仍能下调基因表达。蛋白质印迹分析也证明了P90诱导的CYP 1B 1减少。这些数据表明，P90诱导的BMP 2基因表达的减少可能会干扰吸入有毒化合物的激活和/或解毒能力。
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 μM 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.
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DOI：
10.1165/ajrcmb.25.3.4445
发表时间：
2001-09-01
影响因子：
6.4
作者：
Fujii, T;Hayashi, S;Van Eeden, SF
通讯作者：
Van Eeden, SF
影响因子：
2.1
作者：
Dick, CAJ;Brown, DM;Stone, V
通讯作者：
Stone, V
影响因子：
3.8
作者：
Kanno, Sanae;Furuyama, Akiko;Hirano, Seishiro
通讯作者：
Hirano, Seishiro
影响因子：
10.3
作者：
FOGH, J;WRIGHT, WC;LOVELESS, JD
通讯作者：
LOVELESS, JD
影响因子：
2.1
作者：
Maier, Konrad Ludwig;Alessandrini, Francesca;Schulz, Holger
通讯作者：
Schulz, Holger