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2621818 
Journal Article 
Abstract 
Ultrafine carbon particles down-regulate CYP1B1 expression in human monocytes 
Eder, C; Frankenberger, M; Stanzel, F; Seidel, A; Schramm, K; Ziegler-Heitbrock, L; Hofer, TP 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A1731 
English 
WOS:000208771000731 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
RATIONALE.
Cytochrome P450 monoxygenases (CYP) play important roles 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.

METHODS.
Cells were exposed to various concentrations of ultrafine Printex 90 (P90) particles, TiO2 particles (0.32 to 1,000 µg/ml), and CYP-inducing agent Benzo[a]pyrene (BaP; 0.1 to 10 µM) at different time points (0 to 22h). Expression of CYP enzymes were monitored at the transcriptional and protein level (real time PCR, Western blot).

RESULTS.
In this study we have analyzed the effect of a mixture of fine TiO2 and ultrafine P90 particles P90 on the expression of cytochrome P450 1B1 in human monocytes, macrophages, bronchial epithelial cells and epithelial cell lines. CYP1B1 expression is strongly down-regulated by P90 in monocytes with a maximum effect at 3h after P90 treatment 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. 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.

CONCLUSIONS.
These data suggest that the pronounced P90-induced reduction of CYP gene expression may interfere with the activation and/or detoxification capabilities of inhaled toxic compounds in cells of the lung including monocytes and macrophages. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010