Decreased Cyp2E1 mRNA expression in human leucocytes in patients with fibrotic and inflammatory lung diseases

Abstract

Cytochrome P450 2E1 (CYP2E1), a phase I enzyme, is involved in the activation of a broad spectrum of pro-carcinogens. The importance of this enzyme for pharmacology is derived from its unique substrate spectrum. Large inter-individual differences in the toxicity of its substrates are known. We investigated the quantitative Cyp2E1 mRNA expression in a cohort of patients with fibrotic and inflammatory lung diseases (n=137) and healthy controls (n=221) considering tobacco-smoke, exposure to asbestos, silica, organic dust or chemical irritating particles in relation to the C1053T (RsaI) polymorphism of Cyp2E1. For quantitative comparison of Cyp2E1 mRNA levels real-time PCR was performed using a LightCycler System. Calculations of expression were made with the 2(-DeltaDeltaCT) method. Detection of the C1053T (RsaI) polymorphism of the Cyp2E1 gene was performed by rapid capillary PCR with melting curve analysis. Fibrotic (0.016+/-0.002; n=52; p=0.000) and inflammatory (0.013+/-0.002; n=16, p=0.000) lung disease patients showed a significantly reduced Cyp2E1 mRNA expression compared to healthy controls (0.026+/-0.002; n=206). Exposure to asbestos (0.019+/-0.003; n=40; p=0.016), organic dust (0.016+/-0.003; n=39; p=0.000) and irritative chemicals (0.016+/-0.002; n=22; p=0.000) revealed a highly significant reduced Cyp2E1 expression. Cyp2E1 mRNA expression of occupational disease (OD) patients suffering from lung or pleural asbestosis OD-No. 4103 (0.018+/-0,003; n=31; p=0.024), allergic obstructive airway diseases OD-No. 4301 (0.013+/-0.002; n=23; p=0.000), exogenic allergic alveolitis OD-No. 4201 (0.009+/-0.002; n=6; p=0.000) and obstructive airway diseases caused by irritative chemicals OD-No. 4302 (0.013+/-0.001; n=11; p=0.000) was highly significantly reduced. In conclusion, we demonstrated a significantly decreased mRNA expression in patients with fibrotic and inflammatory lung diseases compared to healthy controls.