Induction of the inflammatory regulator A20 by gibberellic acid in airway epithelial cells

Background and PurposeNF-B-driven inflammation is negatively regulated by the zinc finger protein A20. Gibberellic acid (GA(3)) 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 GA(3) in airway epithelial cells and determine if the anti-inflammatory action relates to A20 induction. Experimental ApproachPrimary nasal epithelial cells and a human bronchial epithelial cell line (16HBE14o-) were used. Cells were pre-incubated with GA(3), stimulated with Pseudomonas aeruginosaLPS; IL-6 and IL-8 release, A20, NF-B and IB expression were then evaluated. To determine if any observed anti-inflammatory effect occurred via an A20-dependent mechanism, A20 was silenced using siRNA. Key ResultsCells pre-incubated with GA(3) had significantly increased levels of A20 mRNA (4h) and protein (24h), resulting in a significant reduction in IL-6 and IL-8 release. This effect was mediated via reduced IB degradation and reduced NF-B (p65) expression. Furthermore, the anti-inflammatory action of GA(3) was abolished in A20-silenced cells. Conclusions and ImplicationsWe showed that A20 induction by GA(3) attenuates inflammation in airway epithelial cells, at least in part through its effect on NF-B and IB. GA(3) or gibberellin-derived derivatives could potentially be developed into anti-inflammatory drugs for the treatment of chronic inflammatory diseases associated with A20 dysfunction. Linked ArticlesThis article is part of a themed section on Inflammation: maladies, models, mechanisms and molecules. To view the other articles in this section visit