@article {Fantauzzi00128-2020, author = {Matthew F. Fantauzzi and Jennifer A. Aguiar and Benjamin J.-M. Tremblay and Michael J. Mansfield and Toyoshi Yanagihara and Abiram Chandiramohan and Spencer Revill and Min Hyung Ryu and Christopher Carlsten and Kjetil Ask and Martin St{\"a}mpfli and Andrew C. Doxey and Jeremy A. Hirota}, title = {Expression of endocannabinoid system components in human airway epithelial cells {\textendash} Impact of sex and chronic respiratory disease status}, elocation-id = {00128-2020}, year = {2020}, doi = {10.1183/23120541.00128-2020}, publisher = {European Respiratory Society}, abstract = {Cannabis smoking is the dominant route of delivery, with the airway epithelium functioning as the site of first contact. The endocannabinoid system is responsible for mediating the physiological effects of inhaled phytocannabinoids. The expression of the endocannabinoid system in the airway epithelium and contribution to normal physiological responses remains to be defined.To begin to address this knowledge gap, a curated dataset of 1090 unique human bronchial brushing gene expression profiles was created. The dataset included 616 healthy subjects, 136 subjects with asthma, and 338 subjects with COPD. A 32-gene endocannabinoid signature was analysed across all samples with sex and disease specific-analyses performed. Immunohistochemistry and immunoblots were performed to probe in situ and in vitro protein expression.CB1, CB2, and TRPV1 protein signal is detectable in human airway epithelial cells in situ and in vitro, justifying examining the downstream endocannabinoid pathway. Sex status was associated with differential expression of 7/32 genes. In contrast, disease status was associated with differential expression of 21/32 genes in asthmatics and 26/32 genes in COPD subjects. We confirm at the protein level that TRPV1, the most differentially expressed candidate in our analyses, was up-regulated in airway epithelial cells from asthmatics relative to healthy subjects.Our data demonstrate that endocannabinoid system is expressed in human airway epithelial cells with expression impacted by disease status and minimally by sex. The data suggest that cannabis consumers may have differential physiological responses in the respiratory mucosa.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. Fantauzzi has nothing to disclose.Conflict of interest: Dr. Aguiar has nothing to disclose.Conflict of interest: Dr. Tremblay has nothing to disclose.Conflict of interest: Dr. Mansfield has nothing to disclose.Conflict of interest: Dr. Yanagihara has nothing to disclose.Conflict of interest: Dr. Chandiramohan has nothing to disclose.Conflict of interest: Dr. Revill has nothing to disclose.Conflict of interest: Dr. Carlsten has nothing to disclose.Conflict of interest: Dr. Ask has nothing to disclose.Conflict of interest: Dr. Doxey has nothing to disclose.Conflict of interest: Dr. Hirota has nothing to disclose.Conflict of interest: Dr. Hyung Ryu has nothing to disclose.Conflict of interest: Dr. Stampfli has nothing to disclose.}, URL = {https://openres.ersjournals.com/content/early/2020/09/24/23120541.00128-2020}, eprint = {https://openres.ersjournals.com/content/early/2020/09/24/23120541.00128-2020.full.pdf}, journal = {ERJ Open Research} }