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Title
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Interleukin-1 alpha induced release of interleukin-8 by human bronchial epithelial cells in vitro : assessing mechanisms and possible treatment options
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Author
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Abstract
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| 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-1 alpha. Our aim is to establish an in vitro model, assess mechanistic pathways and test different therapeutic strategies of IL-1 alpha-induced release of IL-8 by human bronchial epithelial cells. Bronchial epithelial cells (16HBE) were stimulated with IL-1 alpha with or without azithromycin or dexamethasone. IL-8 protein was analyzed in cell supernatant. Different MAP kinases (p38, JNK, ERK1/2, I kappa beta) 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-1 alpha induced IL-8 in bronchial epithelial cells, which was dose-dependently inhibited by dexamethasone but not by azithromycin. IL-1 alpha induced p38 and Akt phosphorylation, but activation of these MAPK was not inhibited by dexamethasone. JNK, ERK1/2, I kappa b and PI3K were not activated. None of the tested drugs reduced the IL-1 alpha induced IL-8 production. We established an in vitro model wherein steroids inhibit the IL-1 alpha-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. |
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Language
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English
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Source (journal)
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Transplant international. - Heidelberg, 1988
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Publication
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Heidelberg
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2017
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ISSN
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0934-0874
[print]
1432-2277
[online]
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DOI
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10.1111/TRI.12915
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Volume/pages
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30
:4
(2017)
, p. 388-397
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ISI
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000397854700007
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Pubmed ID
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28078769
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Full text (Publisher's DOI)
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