Induction of the inflammatory regulator A20 by gibberellic acid in airway epithelial cells
| Autor: | Bettina C. Schock, B Malcomson, S Cheung, Catriona Kelly, Burkhard Hirsch, Agnieszka Czerwiec, Joseph Elborn, R. Barsden, H Dürkop, Madeleine Ennis, James Reihill, A. Bertelsen |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Pharmacology Zinc finger Messenger RNA Regulator RNA Inflammation Biology 03 medical and health sciences IκBα chemistry.chemical_compound Dose–response relationship 030104 developmental biology chemistry immune system diseases hemic and lymphatic diseases Immunology medicine medicine.symptom Gibberellic acid |
| Zdroj: | British Journal of Pharmacology. 173:778-789 |
| ISSN: | 0007-1188 |
| DOI: | 10.1111/bph.13200 |
| Popis: | Background and Purpose NF-κB-driven inflammation is negatively regulated by the zinc finger protein A20. Gibberellic acid (GA3) is a plant-derived diterpenoid with documented anti-inflammatory activity, which is reported to induce A20-like zinc finger proteins in plants. Here, we sought to investigate the anti-inflammatory effect of GA3 in airway epithelial cells and determine if the anti-inflammatory action relates to A20 induction. Experimental Approach Primary nasal epithelial cells and a human bronchial epithelial cell line (16HBE14o-) were used. Cells were pre-incubated with GA3, stimulated with Pseudomonas aeruginosa LPS; IL-6 and IL-8 release, A20, NF-κB and IκBα expression were then evaluated. To determine if any observed anti-inflammatory effect occurred via an A20-dependent mechanism, A20 was silenced using siRNA. Key Results Cells pre-incubated with GA3 had significantly increased levels of A20 mRNA (4 h) and protein (24 h), resulting in a significant reduction in IL-6 and IL-8 release. This effect was mediated via reduced IκBα degradation and reduced NF-κB (p65) expression. Furthermore, the anti-inflammatory action of GA3 was abolished in A20-silenced cells. Conclusions and Implications We showed that A20 induction by GA3 attenuates inflammation in airway epithelial cells, at least in part through its effect on NF-κB and IκBα. GA3 or gibberellin-derived derivatives could potentially be developed into anti-inflammatory drugs for the treatment of chronic inflammatory diseases associated with A20 dysfunction. Linked Articles This article is part of a themed section on Inflammation: maladies, models, mechanisms and molecules. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2016.173.issue-4 |
| Databáze: | OpenAIRE |
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