title: Diminished expression of multidrug resistance-associated protein 1 (MRP1) in bronchial epithelium of COPD patients.
abstract: 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.
authors.affiliation: Department of Medical Oncology, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Margaretha
authors.initials: M
authors.lastname: van der Deen
authors.forename: Hendrik
authors.initials: H
authors.lastname: Marks
authors.forename: Brigitte W M
authors.initials: BW
authors.lastname: Willemse
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.forename: George L
authors.initials: GL
authors.lastname: Scheffer
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000328:Adult; D000368:Aged; D001980:Bronchi / Q000737:chemistry*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1