title: Cytokines and glucocorticoids modulate human bronchial epithelial cell peptidases.
abstract: Peptidases play an important role in the regulation of peptide-mediated effects. Modulation of peptidase activity may therefore be a major mechanism to control peptide actions. Our aim was to analyse the effects of cytokines and glucocorticoids on peptidases expressed by human bronchial epithelial cells, which have been shown to be an important site for peptidase activity. The effects of cytokines [interleukin 1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha), IL-4, interferon gamma (INF-gamma), and epidermal growth factor (EGF)] and/or dexamethasone (DEX) on both expression and activity of neutral endopeptidase (NEP) and aminopeptidase N (APN) by BEAS 2B cells were determined using flow cytometry and activity assays, respectively. IL-1 beta, and to a lesser extent, TNF-alpha and IL-4 increased NEP activity and expression, whereas IFN-gamma decreased NEP. The effect of IL-1 beta was mediated, at least in part, via a cAMP-dependent pathway which did not involve prostaglandin E2 synthesis. APN was increased after 24-h stimulation with IFN-gamma, whereas other stimuli had no effect. DEX strongly increased NEP and APN expression and activity, both in the absence and in the presence of cytokines. We conclude that cytokines and glucocorticoids are able to modulate the activity of NEP and APN on BEAS 2B cells. Our results suggest a role for the human bronchial epithelium in the control of inflammation and indicate that one beneficial effect of glucocorticoids on asthma may be upregulation of peptidases expressed by bronchial epithelial cells.
authors.affiliation: Department of Immunology, Erasmus University, Rotterdam, The Netherlands. vandervelden@immu.fgg.eur.nl
authors.forename: V H
authors.initials: VH
authors.lastname: van der Velden
authors.forename: B A
authors.initials: BA
authors.lastname: Naber
authors.forename: P
authors.initials: P
authors.lastname: van der Spoel
authors.forename: H C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: M A
authors.initials: MA
authors.lastname: Versnel
mesh_terms: D001980:Bronchi / Q000166:cytology; D018826:CD13 Antigens / Q000378:metabolism*; D002452:Cell Count / Q000187:drug effects; D002461:Cell Line, Transformed; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D015260:Neprilysin / Q000378:metabolism*; D015290:Second Messenger Systems
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D018826:CD13 Antigens; D015260:Neprilysin