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Title: Synthetic Response of Stimulated Respiratory Epithelium: Modulation by Prednisolone and iKK2 Inhibition
Authors: Woodman, Lucy Bianca
Wan, Wing Yan Heidi
Milone, Roberta
Grace, Ken
Sousa, Ana
Williamson, Rick
Brightling, Christopher E.
First Published: Jun-2013
Publisher: American College of Chest Physicians (ACCP)
Citation: Chest, 2013, 143 (6), pp. 1656–1666
Abstract: Background: The airway epithelium plays a central role in wound repair and host defense and is implicated in the immunopathogenesis of asthma. Whether there are intrinsic differences between the synthetic capacity of epithelial cells derived from subjects with asthma and healthy control subjects and how this mediator release is modulated by antiinflammatory therapy remains uncertain. We sought to examine the synthetic function of epithelial cells from different locations in the airway tree from subjects with and without asthma and to determine the effects of antiinflamatory therapies upon this synthetic capacity. Methods: Primary epithelial cells were derived from 17 subjects with asthma and 16 control subjects. The release of 13 cytokines and chemokines from nasal, bronchial basal, and air-liquid interface differentiated epithelial cells before and after stimulation with IL-1β, IL-1β and interferon- γ, or Poly-IC (Toll-like receptor 3 agonist) was measured using MesoScale discovery or enzyme-linked immunosorbent assay, and the effects of prednisolone and an inhibitor of nuclear factor κ-B2 (IKK2i) were determined. Results: The pattern of release of cytokines and chemokines was significantly different between nasal, bronchial basal, and differentiated epithelial cells but not between health and disease. Stimulation of the epithelial cells caused marked upregulation of most mediators, which were broadly corticosteroid unresponsive but attenuated by IKK2i. Conclusion: Synthetic capacity of primary airway epithelial cells varied between location and degree of differentiation but was not disease specifi c. Activation of epithelial cells by proinflamatory cytokines and toll-like receptor 3 agonism is attenuated by IKK2i, but not corticosteroids, suggesting that IKK2i may represent an important novel therapy for asthma.
DOI Link: 10.1378/chest.12-1187
ISSN: 0012-3692
eISSN: 1931-3543
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2013 American College of Chest Physicians. This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial License (http://creative com, which permits unrestricted use, distribution, and reproduction to non-commercial entities, provided the original work is properly cited. Information for reuse by commercial entities is available online.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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