The psychoactive substance of cannabis Δ9-tetrahydrocannabinol (THC) negatively regulates CFTR in airway cells
| Autor: | Rachael E. Rayner, Wissam Osman, Xiaoli Zhang, Prosper N. Boyaka, Amal O. Amer, Mark E. Peeples, Jack Wellmerling, Sheng-Wei Chang, Sara Mertz, Estelle Cormet-Boyaka |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway congenital hereditary and neonatal diseases and abnormalities MAP Kinase Signaling System medicine.medical_treatment Biophysics Cystic Fibrosis Transmembrane Conductance Regulator Bronchi Pharmacology Biochemistry 03 medical and health sciences Downregulation and upregulation mental disorders medicine Humans Dronabinol Molecular Biology Cells Cultured Regulation of gene expression Cannabis smoking Lung biology Chemistry organic chemicals Epithelial Cells respiratory system Cystic fibrosis transmembrane conductance regulator respiratory tract diseases ErbB Receptors 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation biology.protein Hallucinogens Homeostasis |
| Zdroj: | Biochimica et biophysica acta. General subjects. 1862(9) |
| ISSN: | 0304-4165 |
| Popis: | Background Marijuana consumption is on the rise in the US but the health benefits of cannabis smoking are controversial and the impact of cannabis components on lung homeostasis is not well-understood. Lung function requires a fine regulation of the ion channel CFTR, which is responsible for fluid homeostasis and mucocilliary clearance. The goal of this study was to assess the effect that exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive substance present in marijuana, has on CFTR expression and function. Methods Cultures of human bronchial epithelial cell line 16HBE14o- and primary human airway epithelial cells were exposed to THC. The expression of CFTR protein was determined by immunoblotting and CFTR function was measured using Ussing chambers. We also used specific pharmacological inhibitors of EGFR and ERK to determine the role of this pathway in THC-induced regulation of CFTR. Results THC decreased CFTR protein expression in primary human bronchial epithelial cells. This decrease was associated with reduced CFTR-mediated short-circuit currents. THC also induced activation of the ERK MAPK pathway via activation of EGFR. Inhibition of EGFR or MEK/ERK prevented THC-induced down regulation of CFTR protein expression. Conclusions and general significance THC negatively regulates CFTR and this is mediated through the EGFR/ERK axis. This study provides the first evidence that THC present in marijuana reduces the expression and function of CFTR in airway epithelial cells. |
| Databáze: | OpenAIRE |
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