Ultrafine carbon particles down-regulate CYP1B1 expression in human monocytes

Eder Christiane, Frankenberger Marion, Stanzel Franz, Seidel Albrecht, Schramm Karl-Werner, Ziegler-Heitbrock Loems, Hofer

Description

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 TiO 2 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 TiO 2 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.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2009
• Nombre de lectures: 25

Extrait

Particle and Fibre Toxicology

BioMedCentral

Open Access Research Ultrafine carbon particles downregulate CYP1B1 expression in human monocytes 1 12,5 3 Christiane Eder, Marion Frankenberger, Franz Stanzel, Albrecht Seidel, 4 11 KarlWerner Schramm, Loems ZieglerHeitbrockand Thomas PJ Hofer*

1 Address: HelmholtzZentrum 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 3 Asklepios Fachkliniken MünchenGauting, RobertKochAllee 2, 82131 Gauting, Germany,Biochemisches Institut für Umweltcarcinogene, 4 Lurup 4, 22927 Grosshansdorf, Germany,Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Institute for 5 Ecological Chemistry, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany andCurrent address: Lungenklinik Hemer, TheoFunccius Strasse 1, 58675 Hemer, Germany

Email: Christiane Eder  christiane.eder@mllonline.de; Marion Frankenberger  frankenberger@helmholtzmuenchen.de; Franz Stanzel  [e-mail]; Albrecht Seidel  albrecht.seidel@biugrimmer.de; KarlWerner Schramm  schramm@helmholtz muenchen.de; Loems ZieglerHeitbrock  zieglerheitbrock@helmholtzmuenchen.de; Thomas PJ Hofer*  hofer@helmholtzmuenchen.de * Corresponding author

Published: 16 October 2009Received: 4 May 2009 Accepted: 16 October 2009 Particle and Fibre Toxicology2009,6:27 doi:10.1186/17438977627 This article is available from: http://www.particleandfibretoxicology.com/content/6/1/27 © 2009 Eder et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background:Cytochrome P450 monoxygenasesplay 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 TiOand ultrafine carbon 2 black Printex 90 particles (P90) on the expression ofcytochrome P450 1B1(CYP1B1) in human monocytes, macrophages, bronchial epithelial cells and epithelial cell lines.CYP1B1expression is strongly downregulated by P90 in monocytes with a maximum after P90 treatment for 3 h while fine and ultrafine TiOhad no effect.CYP1B1was downregulated up to 130fold and in addition 2 CYP1A1mRNA was decreased 13fold. In vitro generated monocytederived macrophages (MDM), epithelial cell lines, and primary bronchial epithelial cells also showed reducedCYP1B1mRNA levels. Benzo[a]pyrene (BaP) is inducingCYB1B1but ultrafine P90 can still downregulate gene expression at 0.1μM of BaP. The P90induced reduction ofCYP1B1was 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.

Background Several epidemiologic studies attribute increased morbid ity and mortality to exposure to environmental particles [13]. These adverse health effects due to the inhalation of

particulate matter are a topic of ongoing scientific and public concern. Particulate matter (PM) is a complex mix ture of many different components, which can be charac terized by origin (anthropogenic or geogenic), by

Page 1 of 13 (page number not for citation purposes)