Elsevier

Cytokine

Volume 10, Issue 1, January 1998, Pages 55-65
Cytokine

Regular article
CYTOKINES AND GLUCOCORTICOIDS MODULATE HUMAN BRONCHIAL EPITHELIAL CELL PEPTIDASES

https://doi.org/10.1006/cyto.1997.0257Get rights and content

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 cytokine and glucocortoids 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 1β (IL-1β), tumour necrosis factor α (TNF-α), IL-4, interferon γ (IFN-γ), 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-1β, and to a lesser extent, TNF-α and IL-4 increased NEP activity and expression, whereas IFN-γ decreased NEP. The effect of IL-1β was mediated, at least in part, via a cAMP-dependent pathway which did not involve prostaglandin E2synthesis. APN was increased after 24-h stimulation with IFN-γ, 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.

References (0)

Cited by (43)

  • Temporal changes in neutral endopeptidase/CD10 immunoexpression in the cyclic and early pregnant canine endometrium

    2014, Theriogenology
    Citation Excerpt :

    CD10 functions as a cell-surface enzyme acting to reduce the cell response to some peptide factors, including oxytocin, endothelins, and interleukin 1 [12]; through cleavage and inactivation of these peptides, NEP/CD10 reduces its local concentrations and decreases their effects [13-15]. NEP/CD10 has been implicated in the regulation of growth and differentiation in many cellular systems, in which it plays an important role in the maintenance of homeostasis [16–18] and in carcinogenesis and tumor progression [19–23], possibly mediated through its role on angiogenesis [24], in cell cycle activity [25], and apoptosis [26]. In human, NEP/CD10 is frequently used as a reliable immunohistochemical marker of normal endometrial stroma [27,28] and is used for diagnosis of several neoplasic [28–30] and non-neoplasic [31,32] gynecological conditions.

  • Noradrenaline deficiency in brain increases β-amyloid plaque burden in an animal model of Alzheimer's disease

    2007, Neurobiology of Aging
    Citation Excerpt :

    Changes in NEP expression have also been reported in response to several inflammatory mediators. In a bronchial epithelial cell line, IL1β, and to a lesser extent TNFα, increased NEP protein expression while IFNγ decreased it [45]. Interestingly, in the same study NEP expression was increased by the cAMP analog dbcAMP, while incubation with a phosphodiesterase inhibitor potentiated the increase due to IL1β.

View all citing articles on Scopus
f1

Correspondence to: V.H.J. van der Velden, Department of Immunology, Erasmus Univesity Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands: E-mail: [email protected]

f2

Phone: 0171-2674466

f3

Phone: 0171-2674466

View full text