Xenobiotic metabolism enzyme gene expression in human bronchial epithelial and alveolar macrophage cells.
Human bronchial epithelial cells (BEC), a primary defense against inhaled materials, are the progenitor cells for bronchogenic carcinomas and have important metabolic capabilities. We used reverse transcriptase-polymerase chain reaction (RT-PCR) to identify xenobiotic metabolism enzymes expressed in primary BEC and alveolar macrophages (AM) of non-smoking volunteers. Cytochromes P450 (CYP) 1A1, 1B1, 2B7, 2E1, and 4B1 and microsomal epoxide hydrolase (mEH) were expressed in BEC but not AM. CYP2F1 was expressed in BEC, but it was expressed at barely detectable levels or not at all in AM. NADPH oxidoreductase (NADPH OR), microsomal glutathione transferase (GST 12), glutathione transferase mu, phenol sulfotransferase (PST), thermolabile phenol sulfotransferase (TL PST), and the clara cell-specific gene, CC10 were expressed in both BEC and AM. CYP3A4 and glucuronosyl transferases-1 and 2 were not expressed in either BEC or AM. In contrast to primary BEC, of the genes evaluated, the immortalized human bronchial epithelial cell line BEP2D constitutively expressed only CYP1A1, CYP2E1, NADPH OR, glucuronosyl transferase 1, GST 12, GST mu, PST, TL PST, and CC10. The loss of xenobiotic metabolism enzyme gene expression in the BEP2D cell line may result from either reduced exposure to inducing agents, or loss of differentiative characteristics in culture. It is clear from the data comparing BEC and AM that there are important intertissue differences in expression of xenobiotic metabolism enzymes.
Willey
J C
JC
Department of Medicine, Medical College of Ohio, Toledo, USA.
Coy
E
E
Brolly
C
C
Utell
M J
MJ
Frampton
M W
MW
Hammersley
J
J
Thilly
W G
WG
Olson
D
D
Cairns
K
K
D001483:Base Sequence; D001980:Bronchi / Q000166:cytology / Q000201:enzymology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014166:Transferases / Q000235:genetics; D014598:Uteroglobin; D015262:Xenobiotics / Q000378:metabolism*
D011506:Proteins; D012333:RNA, Messenger; C556389:SCGB1A1 protein, human; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D014598:Uteroglobin; D009247:NADH, NADPH Oxidoreductases; D014166:Transferases; D004851:Epoxide Hydrolases