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Cytochrome P450 monooxygenases expression in human epithelial lung cell lines

 
: Niehof, Monika; Hansen, Tanja

The Toxicologist 52 (2013), No.1, pp.59, Abstract PS 282
ISSN: 0731-9193
Society of Toxicology (Annual Meeting) <52, 2013, San Antonio/Tex.>
English
Journal Article, Conference Paper
Fraunhofer ITEM ()

Abstract
The pulmonary epithelium is the first barrier for airborne xenobiotics and inhaled drugs. Cytochrome P450 monooxygenases (CYP) participate in metabolic inactivation of xenobiotics. Beyond that some compounds require enzymatic activation to exert their toxic effects or their desirable functions. The bronchiale epithelial cell line Calu-3 and the type II-like pulmonary epithelial cell line A549 serve as cell culture models for the human respiratory epithelium. So far, there is little information regarding their metabolic properties especially for Calu-3 cells. The goal of this study was to further characterize both cell lines regarding their basal and inducible CYP isoform expression.
CYP expression was determined using real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR). Basal expression of CYP1B1, CYP1A1, CYP2D6, CYP2B6/7, CYP3A5, and CYP2J2, and slight amounts of further CYPs were detected in both cell lines, which is consistent with expression in the human lung.
Furthermore, potential CYP inducers were analyzed. Omeprazole acts on aryl hydrocarbon receptor (AhR) activation and induced CYP1A1 and CYP1B1 in both cell lines. Rifampicin acts on pregnane x receptor (PXR) and henobarbitale acts predominantly on constitutive androstane receptor (CAR), however, both receptors are not expressed in the lung. Accordingly, both agents did not induce any CYP in these cells. Besides PXR, examethasone acts on glucocorticoid receptors and we found induction of members of the CYP3A family, mainly CYP3A7 in Calu-3 cells, and CYP3A5 and CYP3A7 in A549 cells. CITCO is known to act as a CAR agonist and is normally used to induce CYP2B6/7. However, it is a potent inducer of CYP1B1 in Calu-3 cells, and of CYP1A1 and CYP1B1 in A549 cells. Thus, Calu-3 cells and A549 cells express a broad range of CYPs with preserved inducibility and are valuable models of the airway epithelial barrier for metabolic in vitro experiments.

: http://publica.fraunhofer.de/documents/N-275951.html