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

ABSTRACT:

Background and purpose

NF-?B-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-?B and I?B? 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 I?B? degradation and reduced NF-?B (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-?B and I?B?. GA3 or gibberellin-derived derivatives could potentially be developed into anti-inflammatory drugs for the treatment of chronic inflammatory diseases associated with A20 dysfunction.

SUBMITTER: Reihill JA 

PROVIDER: S-EPMC4742295 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature