Induction and regulation of xenobiotic-metabolizing cytochrome P450s in the XXXX A549 lung adenocarcinoma cell line.

@entity1 @entity4187 @entity670 @entity5322 @entity5396 @entity4188 @entity29478 @entity619 @entity109 @entity866 @entity1300 @entity669 @entity420 @entity18398
Several cytochrome P450 (CYP) enzymes are expressed in the @entity1 lung, where they participate in metabolic inactivation and activation of numerous exogenous and endogenous compounds. In this study, the expression pattern of all known xenobiotic-metabolizing CYP genes was characterized in the @entity1 alveolar type II cell-derived A549 @entity420 cell line using qualitative reverse transcriptase/polymerase chain reaction (RT-PCR). In addition, the mechanisms of induction by chemicals of members in the @entity4187 and @entity5322 subfamilies were assessed by quantitative RT-PCR. The expression of messenger RNAs (mRNAs) of CYPs 1A1, 1B1, 2B6, 2C, 2E1, 3A5, and 3A7 was detected in the A549 cells. The amounts of mRNAs of CYPs 1A2, 2A6, 2A7, 2A13, 2F1, 3A4, and 4B1 were below the limit of detection. @entity1300 ( @entity1300 ) induced @entity4187 and @entity4188 mRNAs 56-fold and 2.5-fold, respectively. @entity5396 was induced 8-fold by @entity619 and 11-fold by @entity109 . @entity5322 was not induced by any of the typical @entity5322 inducers used. The @entity669 kinase inhibitor @entity670 and the protein kinase C inhibitor @entity866 blocked @entity1300 -elicited induction of @entity4187 , but they did not affect @entity4188 induction. Protein phosphatase inhibitors @entity18398 and @entity29478 enhanced @entity1300 -induction of @entity4188 slightly, but had negligible effects on @entity4187 induction. These results suggest that @entity4187 and @entity4188 are differentially regulated in @entity1 pulmonary epithelial cells and give the first indication of the induction of @entity5396 by glucocorticoids in @entity1 lung cells. These results establish that having retained several characteristics of @entity1 lung epithelial cell CYP expression, the A549 lung cell line is a valuable model for mechanistic studies on induction of the pulmonary CYP system.
