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Cytochrome P450 monooxygenases expression in human bronchial epithelial calu-3 cells under different culture conditions

: Hansen, Tanja

The Toxicologist 53 (2014), Nr.1, S.133, PS 512
ISSN: 0731-9193
Society of Toxicology (Annual Meeting) <53, 2014, Phoenix/Ariz.>
Fraunhofer ITEM ()

The pulmonary epithelium is the first barrier for airborne xenobiotics and inhaled drugs and the cell line Calu-3 is a well characterized model for in vitro tracheobronchial epithelial permeability. To serve as a model for toxicity testing of airborne substances (gases, aerosols, particles), Calu-3 cells can be cultured under air interfaced culture (AIC) conditions. However, there is little information regarding the metabolic properties of Calu-3 cells under AIC conditions compared to conventional liquid covered culture (LCC) conditions. It was thus the goal of this study to characterize the basal and inducible cytochrome P450 (CYP) isoform expression in Calu-3 cells under AIC and LCC conditions. Calu-3 cells were cultured under AIC and LCC conditions and induction experiments were started on day 11 after passage. The transepithelial electrical resistance (TEER) was measured to monitor the barrier properties of the cell monolayers. CYP expression was determined using real-time reverse transcription quantitative polymerase chain reaction (RTqPCR). Comparable basal expression of CYP1B1, CYP2B6/7, CYP2J2, CYP2C, CYP2E1, CYP2D6, CYP1A1, CYP3A4, CYP3A5 and CYP3A7 was detected under both conditions, which is consistent with expression in the human lung. Omeprazole, a well-known activator of the aryl hydrocarbon receptor (AhR) induced CYP1A1 and CYP1B1 in Calu-3 cells under both conditions, with stronger induction being observed in AIC cultures. Dexamethasone acts via glucocorticoid receptors and we found slight but significant induction of CYP3A4 and CYP3A5 in LCC cultures only. In summary, Calu-3 cells express a broad range of CYPs under both culture conditions with preserved inducibility for the main lung CYPs 1A1 and 1B1 and are thus a valuable model of the airway epithelial barrier for in vitro toxicity testing of airborne substances.