Ultrafine carbon particles down-regulate CYP1B1 expression in human monocytes

• Main Authors: Ziegler-Heitbrock Loems, Seidel Albrecht, Schramm Karl-Werner, Stanzel Franz, Frankenberger Marion, Eder Christiane, Hofer Thomas PJ
• Format: Article
• Language: English
• Published: BMC 2009-10-01
• Series: Particle and Fibre Toxicology
• Online Access: http://www.particleandfibretoxicology.com/content/6/1/27

<p>Abstract</p> <p>Background</p> <p><it>Cytochrome P450 monoxygenases </it>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.</p> <p>Results</p> <p>In this study we have analyzed the effect of a mixture of fine TiO₂and ultrafine carbon black Printex 90 particles (P90) on the expression of <it>cytochrome P450 1B1 </it>(<it>CYP1B1</it>) in human monocytes, macrophages, bronchial epithelial cells and epithelial cell lines. <it>CYP1B1 </it>expression is strongly down-regulated by P90 in monocytes with a maximum after P90 treatment for 3 h while fine and ultrafine TiO₂had no effect. <it>CYP1B1 </it>was down-regulated up to 130-fold and in addition <it>CYP1A1 </it>mRNA was decreased 13-fold. In vitro generated monocyte-derived macrophages (MDM), epithelial cell lines, and primary bronchial epithelial cells also showed reduced <it>CYP1B1 </it>mRNA levels. Benzo[<it>a</it>]pyrene (BaP) is inducing <it>CYB1B1 </it>but ultrafine P90 can still down-regulate gene expression at 0.1 μM of BaP. The P90-induced reduction of <it>CYP1B1 </it>was also demonstrated at the protein level using Western blot analysis.</p> <p>Conclusion</p> <p>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.</p>