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Expression of cytochrome P450 mRNA s in Type II alveolar cells from subjects with chronic obstructive pulmonary disease

2018; Wiley; Volume: 6; Issue: 3 Linguagem: Inglês

10.1002/prp2.405

2052-1707

Satoshi Kamata, Naoya Fujino, Mitsuhiro Yamada, Ken Grime, Satoshi Suzuki, Chiharu Ota, Yukiko Tando, Yoshinori Okada, Akira Sakurada, Masafumi Noda, Yasushi Matsuda, Hisatoshi Sugiura, Masakazu Ichinose,

Receptor Mechanisms and Signaling

Abstract Inhaled drugs are critical for the treatment of inflammatory airway diseases such as chronic obstructive pulmonary disease ( COPD ). To develop better therapeutics for pulmonary disease it is of potential importance to understand molecular mechanisms of local biotransformation in the lung. Alveolar epithelial type II ( ATII ) cells have a key role in homeostasis in the lung, but little is known about expression patterns of genes encoding cytochrome P450 ( CYP ) enzymes in ATII cells. In addition, alteration of CYP gene expression has not been fully defined in COPD . We previously established a method to purify ATII cells from the adult human lung using fluorescence‐activated cell sorting. By employing this technique we determined gene expression patterns of 14 CYP enzymes in ATII cells from nonsmokers (n = 4) and smokers (n = 4), both having normal pulmonary function. Although most CYP genes are highly expressed in primary hepatocytes, we found that CYP 1B1 mRNA expression was 7.2‐fold higher in ATII compared to hepatocytes ( P = .0275). Additionally we noted a 3.0‐fold upregulation of CYP 2C19 and 50% reduction in CYP 2J2 mRNA expressions in ATII cells isolated from patients with COPD (n = 3) compared to smokers without COPD (n = 4). These data, for the first time, detail a comprehensive set of genes encoding CYP enzymes in human ATII cells and highlights differentially expressed CYP mRNA s of patients with COPD . Such understanding may have important implications for the development of novel inhaled drugs.