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Biochem Pharmacol. 2016 Nov 15;120:63-71. doi: 10.1016/j.bcp.2016.09.008. Epub 2016 Sep 15.

Δ9-Tetrahydrocannabinol reverses TNFα-induced increase in airway epithelial cell permeability through CB2 receptors.

Author information

1
Cell Signalling and Pharmacology Research Group, School of Life Sciences, University of Nottingham, Medical School, Nottingham NG7 2UH, UK.
2
Cell Signalling and Pharmacology Research Group, School of Life Sciences, University of Nottingham, Medical School, Nottingham NG7 2UH, UK. Electronic address: richard.roberts@nottingham.ac.uk.

Abstract

Despite pharmacological treatment, bronchial hyperresponsiveness continues to deteriorate as airway remodelling persists in airway inflammation. Previous studies have demonstrated that the phytocannabinoid Δ9-tetrahydrocannabinol (THC) reverses bronchoconstriction with an anti-inflammatory action. The aim of this study was to investigate the effects of THC on bronchial epithelial cell permeability after exposure to the pro-inflammatory cytokine, TNFα. Calu-3 bronchial epithelial cells were cultured at air-liquid interface. Changes in epithelial permeability were measured using Transepithelial Electrical Resistance (TEER), then confirmed with a paracellular permeability assay and expression of tight junction proteins by Western blotting. Treatment with THC prevented the TNFα-induced decrease in TEER and increase in paracellular permeability. Cannabinoid CB1 and CB2 receptor-like immunoreactivity was found in Calu-3 cells. Subsequent experiments revealed that pharmacological blockade of CB2, but not CB1 receptor inhibited the THC effect. Selective stimulation of CB2 receptors displayed a similar effect to that of THC. TNFα decreased expression of the tight junction proteins occludin and ZO-1, which was prevented by pre-incubation with THC. These data indicate that THC prevents cytokine-induced increase in airway epithelial permeability through CB2 receptor activation. This highlights that THC, or other cannabinoid receptor ligands, could be beneficial in the prevention of inflammation-induced changes in airway epithelial cell permeability, an important feature of airways diseases.

KEYWORDS:

ACEA (PubChem CID: 5311006); AM251 (PubChem CID: 2125); Airway; Cannabinoid receptors; Epithelium; HU-210 (PubChem CID: 9821569); JWH133 (PubChem CID: 6918505); SR144528 (PubChem CID: 3081355); THC; Tight junctions; Δ(9)-tetrahydrocannabinol (PubChem CID: 16078)

PMID:
27641813
DOI:
10.1016/j.bcp.2016.09.008
[Indexed for MEDLINE]

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