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- Title
Interleukin-1α induced release of interleukin-8 by human bronchial epithelial cells in vitro: assessing mechanisms and possible treatment options.
- Authors
Bellon, Hannelore; Vandermeulen, Elly; Mathyssen, Carolien; Sacreas, Annelore; Verleden, Stijn E; Heigl, Tobias; Vriens, Hanne; Lammertyn, Elise; Pilette, Charles; Hoet, Peter; Vos, Robin; Vanaudenaerde, Bart M; Verleden, Geert M
- Abstract
Survival after lung transplantation is hampered by chronic lung allograft dysfunction ( CLAD). Persistently elevated BAL-neutrophilia is observed in some patients despite treatment with azithromycin, which may be induced by IL-1α. Our aim is to establish an in vitro model, assess mechanistic pathways and test different therapeutic strategies of IL-1α-induced release of IL-8 by human bronchial epithelial cells. Bronchial epithelial cells (16 HBE) were stimulated with IL-1α with or without azithromycin or dexamethasone. IL-8 protein was analyzed in cell supernatant. Different MAP kinases (p38, JNK, ERK1/2, Iκβ) and targets known to be involved in tumor formation ( PI3K, Akt) were investigated. Finally, different treatment options were tested for their potential inhibitory effect. IL-1α induced IL-8 in bronchial epithelial cells, which was dose-dependently inhibited by dexamethasone but not by azithromycin. IL-1α induced p38 and Akt phosphorylation, but activation of these MAPK was not inhibited by dexamethasone. JNK, ERK1/2, Iκβ and PI3K were not activated. None of the tested drugs reduced the IL-1α induced IL-8 production. We established an in vitro model wherein steroids inhibit the IL-1α-induced IL-8 production, while azithromycin was ineffective. Despite using this simple in vitro model, we could not identify a new treatment option for azithromycin-resistant airway neutrophilia.
- Subjects
LUNG transplantation; AZITHROMYCIN; IMMUNOSUPPRESSION; EPITHELIAL cells; TUMOR growth; PATIENTS; TRANSPLANTATION of organs, tissues, etc.; THERAPEUTICS
- Publication
Transplant International, 2017, Vol 30, Issue 4, p388
- ISSN
0934-0874
- Publication type
Article
- DOI
10.1111/tri.12915