Induction of the inflammatory regulator A20 by gibberellic acid in airway epithelial cells. (21st July 2015)

• Record Type: Journal Article
• Authors: 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
• Other Names: Stewart AG guestEditor.; Beart PM guestEditor.
• Is Part Of: British journal of pharmacology. Volume 173:Number 4(2016:Feb.)
• Page Start: 778
• Page End: 789
• Publication Date: 2015-07-21
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.13200
• Languages: English
• ISSNs: 0007-1188

Abstract

Abstract : 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 P seudomonas 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 visithttp://dx.doi.org/10.1111/bph.2016.173.issue-4