Due to the similarity of the CYP expression patterns, alveolar macrophages are better surrogate cells for lung tissue than peripheral blood lymphocytes. Alveolar macrophages expressed mRNAs of CYP2B6, CYP2C, CYP3A5, and CYP4B1, which have not been demonstrated before.
CYP3A5 is the main CYP3A form in human lung. It was expressed in every sample, while CYP3A4 was expressed in about 20% of cases. CYP3A5 was expressed in bronchial, bronchiolar, and alveolar epithelium as well as in endothelium and alveolar macrophages.
Both the expression pattern and the induction profile of CYPs in the A549 cell line were found to be reasonably similar to those seen in human lung tissue. These findings establish this cell line as a good model for mechanistic studies on pulmonary CYP enzymes.
CYP1A1 induction by TCDD was regulated by phosphorylation similarly in A549 cells as in other human cell models. The regulation of TCDD-elicited induction of CYP1B1 was different compared to CYP1A1.
CYP3A5 induction by inhaled glucocorticoids was mediated by glucocorticoid receptor, and induction was achieved at low nanomolar concentrations, which makes it feasible for this induction to occur in the bronchial epithelium of patients using inhaled glucocorticoids. However, inhaled glucocorticoids were not found to induce CYP3A5 in human alveolar macrophages in vivo.
Smoking decreased the CYP3A5 mRNA level in alveolar macrophages.