| Autor: |
Reihill, J. A., Malcomson, B, Bertelsen, A., Cheung, S, Czerwiec, Agnieszka, Barsden, R, Elborn, J S, Dürkop, H, Hirsch, B, Ennis, M, Kelly, C, Schock, B C |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Reihill, J A, Malcomson, B, Bertelsen, A, Cheung, S, Czerwiec, A, Barsden, R, Elborn, J S, Dürkop, H, Hirsch, B, Ennis, M, Kelly, C & Schock, B C 2016, ' Induction of the inflammatory regulator A20 by gibberellic acid in airway epithelial cells ', British Journal of Pharmacology, vol. 173, no. 4, pp. 778-789 . https://doi.org/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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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