title: Enhanced expression of neutral endopeptidase (NEP) in airway epithelium in biopsies from steroid- versus nonsteroid-treated patients with atopic asthma.
abstract: The expression of the endogenous neuropeptide-degrading enzyme, neutral endopeptidase (NEP; CALLA, CD10, E.C.3.4.24.11) on cultured human airway epithelial cells can be upregulated by corticosteroids. We examined whether NEP expression in the airway epithelium or lamina propria in bronchial biopsies is enhanced in atopic asthmatics on regular inhaled steroids as compared with those without steroid treatment. Forty nonsmoking adults (age 19 to 48 yr) with mild to moderate asthma (forced expiratory volume in 1 s > or = 50% pred., histamine PC20 range 0.02 to 7.6 mg/ml) with (n = 23) or without (n = 17) regular inhaled steroids treatment entered the study. Biopsies were taken at (sub)segmental level from the right lower lobe, the middle lobe, and the main carina. Immunohistochemical staining was performed on cryostat sections using the VIL-A1 monoclonal antibody against CD10 (NEP). Intra- and inter-observer repeatability of a semiquantitative scoring method was good as assessed by weighted kappa (kappa(w) ranging from 0.66 to 0.81). In the airway epithelium, NEP-positive sites were within the basal layer and, in contrast with studies applying other antibodies, also at apical sites and within the lamina propria. In both the epithelium and lamina propria, NEP expression was not significantly different between the three biopsy sites (Friedman's nonparametric two-way analysis of variance; P > 0.68), nor was expression in the lamina propria associated with inhaled steroid usage (Mann-Whitney U test; P = 0.98). However, NEP expression was significantly enhanced in the airway epithelium in patients using inhaled steroids as compared with nonsteroid users (mean rank: 23.4 and 15.5, respectively; P = 0.02). Among nonsteroid-using subjects, NEP expression was related to symptoms and the methacholine PC20 (Rs: -0.69 and 0.49, respectively; P < or = 0.04). We conclude that the expression of NEP is enhanced in airway epithelium in bronchial biopsy specimens from patients with atopic asthma who are regularly using inhaled steroids as compared with patients who do not. This fits the hypothesis that the anti-inflammatory effect of corticosteroids within the airways is partially mediated by the upregulation of the endogenous neuropeptide-degrading enzyme NEP.
authors.affiliation: Department of Pulmonology, Leiden University Medical Centre, the Netherlands.
authors.forename: J K
authors.initials: JK
authors.lastname: Sont
authors.forename: J H
authors.initials: JH
authors.lastname: van Krieken
authors.forename: H C
authors.initials: HC
authors.lastname: van Klink
authors.forename: A C
authors.initials: AC
authors.lastname: Roldaan
authors.forename: C R
authors.initials: CR
authors.lastname: Apap
authors.forename: L N
authors.initials: LN
authors.lastname: Willems
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
mesh_terms: D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D001507:Beclomethasone / Q000627:therapeutic use; D001980:Bronchi / Q000201:enzymology*; D019819:Budesonide; D003430:Cross-Sectional Studies; D004848:Epithelium / Q000201:enzymology; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000032:analysis*; D015588:Observer Variation; D010366:Peak Expiratory Flow Rate; D011282:Pregnenediones / Q000627:therapeutic use
chemical_list: D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D011282:Pregnenediones; D019819:Budesonide; D006632:Histamine; D015260:Neprilysin; D001507:Beclomethasone