Expression of endocannabinoid system components in human airway epithelial cells: impact of sex and chronic respiratory disease status

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.

Development and validation of a mouse model of contemporary cannabis smoke exposure

“…This in-house method is scalable to other research labs. In addition, we assessed both male and female mice, given the growing body of evidence that sex differences play an integral role in cannabis metabolism and cannabinoid signaling [36][37][38] . We suggest that future cannabis studies should aim to provide at minimum the strain name and THC and CBD concentrations to enable comparison between studies.…”

Cannabinoids and Inflammations of the Gut-Lung-Skin Barrier

“…Both CB1 and CB2 receptors are expressed by eosinophils, monocytes and monocyte-derived macrophages [99,105]. CB1, CB2 and TRPV1 have been identified in situ and in vitro at the protein level in airway epithelial cells; however, the impact of these findings on the biology of respiratory inflammations remains unclear [106].…”

Development and validation of a mouse model of contemporary cannabis smoke exposure

“…This in-house method is scalable to other research labs. In addition, we assessed both male and female mice, given the growing body of evidence that sex differences play an integral role in cannabis metabolism and cannabinoid signaling [33][34][35] . With these experimental variables implemented, our cannabis smoke exposure system effectively models real-world cannabis use patterns while respecting the need for reliability in a research environment.…”