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Decreased Cyp2E1 mRNA expression in human leucocytes in patients with fibrotic and inflammatory lung diseases
Simone Helmig1, Juliane Döhrel, Joachim Schneider
1Institut und Poliklinik für Arbeits- und Sozialmedizin, der Justus-Liebig Universität, D-35392 Giessen, Germany. simone.helmig@arbmed.med.uni-giessen.de
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.
Insights
This study found significantly reduced Cytochrome P450 2E1 (CYP2E1) mRNA expression in patients with fibrotic and inflammatory lung diseases. These findings highlight CYP2E1
Area of Science:
- Biochemistry
- Toxicology
- Pulmonology
Background:
- Cytochrome P450 2E1 (CYP2E1) is a phase I enzyme crucial for activating pro-carcinogens.
- Significant inter-individual variability exists in CYP2E1 substrate toxicity.
- Understanding CYP2E1 expression is vital for pharmacology and occupational lung disease research.
Purpose of the Study:
- To quantify CYP2E1 mRNA expression in patients with fibrotic and inflammatory lung diseases.
- To investigate the influence of occupational exposures (tobacco smoke, asbestos, silica, organic dust, chemical irritants) on CYP2E1 expression.
- To examine the association between the CYP2E1 C1053T polymorphism and mRNA levels.
Main Methods:
- Real-time PCR (LightCycler System) was used for quantitative CYP2E1 mRNA expression analysis.
- The 2(-DeltaDeltaCT) method was employed for expression calculations.
- Capillary PCR with melting curve analysis was performed to detect the CYP2E1 C1053T polymorphism.
Main Results:
- Patients with fibrotic and inflammatory lung diseases exhibited significantly reduced CYP2E1 mRNA expression compared to healthy controls.
- Exposure to asbestos, organic dust, and chemical irritants was associated with highly significant reductions in CYP2E1 expression.
- Specific occupational diseases, including asbestosis and obstructive airway diseases, showed markedly decreased CYP2E1 mRNA levels.
Conclusions:
- A significant decrease in CYP2E1 mRNA expression is demonstrated in patients suffering from fibrotic and inflammatory lung diseases.
- Occupational exposures contribute to altered CYP2E1 expression patterns in lung disease patients.
- These findings underscore the role of CYP2E1 in the pathophysiology of occupational and environmental lung diseases.
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