Cigarette smoke is the principal risk factor for chronic obstructive pulmonary disease (COPD). Multidrug resistance proteins, such as multidrug resistance-associated protein-1 (MRP1), P-glycoprotein (P-gp), and lung resistance-related protein (LRP), may protect against oxidative stress and toxic compounds generated by cigarette smoking. Expression of MRP1, P-gp, and LRP was evaluated in bronchial epithelium of two study groups of COPD patients and their controls and was associated with disease status and smoking history. In study group 1, MRP1, but not P-gp and LRP expression, was lower (p=0.029) in normal bronchial epithelium of COPD patients (n=11) compared to healthy controls (n=8). MRP1 expression was high in squamous metaplastic epithelium. When including expression in squamous metaplastic cells, MRP1 was still lower in total bronchial epithelium in the COPD group (p=0.038). In study group 2, expression of MRP1, but not of P-gp and LRP, was lower (p=0.047) in lung tissue of (very) severe COPD (n=10) vs mild to moderate COPD (n=9) patients. In conclusion, MRP1 expression was lower in bronchial biopsies of COPD patients than of healthy controls and was also lower in patients with severe COPD than with mild/moderate COPD. Our findings indicate that diminished MRP1 expression in normal bronchial epithelium is associated with COPD. The exact role in COPD pathogenesis is to be revealed by further functional studies.
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This work was supported by a grant from the Netherlands Asthma Foundation (NAF 97.35). The authors thank Dr. W.J. Sluiter for the critical evaluation of statistical analyses and Mrs. Adriana Pijnenborg for the excellent technical support. The authors declare that their experiments comply with the current laws of the country in which they were performed (i.e., the Netherlands).
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van der Deen, M., Marks, H., Willemse, B.W.M. et al. Diminished expression of multidrug resistance-associated protein 1 (MRP1) in bronchial epithelium of COPD patients. Virchows Arch 449, 682–688 (2006). https://doi.org/10.1007/s00428-006-0240-3
- Chronic obstructive pulmonary disease