Research
Ultrafine carbon particles down-regulate CYP1B1 expression in human monocytes
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* Corresponding author: Thomas PJ Hofer hofer@helmholtz-muenchen.de
1 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
2 Asklepios Fachkliniken München-Gauting, Robert-Koch-Allee 2, 82131 Gauting, Germany
3 Biochemisches Institut für Umweltcarcinogene, Lurup 4, 22927 Grosshansdorf, Germany
4 Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Institute for Ecological Chemistry, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany
5 Current address: Lungenklinik Hemer, Theo-Funccius-Strasse 1, 58675 Hemer, Germany
Particle and Fibre Toxicology 2009, 6:27 doi:10.1186/1743-8977-6-27
Published: 16 October 2009Abstract
Background
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.
Results
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.
Conclusion
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.