The endogenous cannabinoid anandamide increases human airway epithelial cell permeability through an arachidonic acid metabolite

Shang, V.C.M.; O'Sullivan, Saoirse; Kendall, D.A.; Roberts, Richard E.

Abstract

Injury to the bronchial epithelium in respiratory diseases such as asthma and COPD results in the lossof barrier function and an elevated sensitivity to environmental insults. An increased release of theendogenous cannabinoid, anandamide in response to inhalation of allergen in asthmatic patients hasbeen reported. The aim of this study was, therefore, to determine the effects of endocannabinoids onbronchial epithelial cell permeability and to investigate the mechanisms involved.Calu-3 human bronchial epithelial cells were cultured at air–liquid interface to allow developmentof tight junctions. Changes in Transepithelial Electrical Resistance (TEER), a reflection of epithelial per-meability, were measured at various time points post-treatment, and expression of the tight junctionproteins, occludin and ZO-1, were determined using Western immunoblotting.Anandamide produced a significant reduction in TEER, which was unaffected by cannabinoid receptorantagonists, but attenuated by URB597, an inhibitor of fatty acid amide hydrolase, and by a combinationof cyclooxygenase (COX) and lipoxygenase (LOX) blockade. The anandamide metabolite, arachidonicacid, showed similar TEER decrease that was also prevented in the presence of COX and LOX inhibitor.Expression of occludin and ZO-1 were also reduced by anandamide.These findings indicate a pro-inflammatory-like effect of anandamide on bronchial epithelial per-meability, mediated by cyclooxygenase and lipoxygenase metabolites, and suggest that inhibition ofanandamide degradation might provide a novel approach to treat airway inflammation.

Citation

Shang, V., O'Sullivan, S., Kendall, D., & Roberts, R. E. (2016). The endogenous cannabinoid anandamide increases human airway epithelial cell permeability through an arachidonic acid metabolite. Pharmacological Research, 105, https://doi.org/10.1016/j.phrs.2016.01.023

• Journal Article Type: Article
• Acceptance Date: Jan 19, 2016
• Online Publication Date: Jan 22, 2016
• Publication Date: Mar 2, 2016
• Deposit Date: Aug 3, 2016
• Journal: Pharmacological Research
• Print ISSN: 1043-6618
• Electronic ISSN: 1096-1186
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 105
• DOI: https://doi.org/10.1016/j.phrs.2016.01.023
• Keywords: Anandamide; Bronchial epithelium; Chronic airway inflammation; Endocannabinoid; Permeability; Tight junction
• Public URL: https://nottingham-repository.worktribe.com/output/781858
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S1043661816000256
• Contract Date: Aug 3, 2016