Expression of the endocannabinoid system in the human airway epithelial cells – Impact of sex and chronic respiratory disease status
Bibliographic record
Abstract
ABSTRACT Recreational and medicinal cannabis consumption in the past 12 months has been reported in 1/5 th of Canadians, with greater use in males relative to females. Cannabis smoking is the dominant route of delivery in consumers, with the airway epithelium functioning as the site of first contact for inhaled phytocannabinoids. The endocannabinoid system is responsible for mediating the physiological effects of inhaled phytocannabinoids. Acute cannabis smoke inhalation can result in bronchodilation, which may have applications in chronic respiratory disease management. In contrast, chronic cannabis smoke inhalation is associated with reduced lung function and bronchitis, which challenges potential applications in the lung. The contribution of the endocannabinoid system in the airway epithelium to either beneficial or harmful physiological responses remains to be clearly defined in males and females and those with underlying chronic respiratory disease. To begin to address this knowledge gap, a curated dataset of 1090 unique human bronchial brushing gene expression profiles was created from Gene Expression Omnibus deposited microarray datasets. The dataset included 616 healthy subjects, 136 subjects with asthma, and 338 subjects with COPD. A 27-gene endocannabinoid signature was analyzed across all samples with sex and disease specific-analyses performed. Immunohistochemistry and immunoblots were performed to confirm in situ and in vitro protein expression of select genes in human airway epithelial cells. We confirm three receptors for cannabinoids, CB 1 , CB 2 , and TRPV1, are expressed at the protein level in human airway epithelial cells in situ and in vitro , justifying examining the downstream endocannabinoid pathway more extensively at the gene expression level. Sex status was associated with differential expression of 6/27 genes. In contrast, disease status was associated with differential expression of 18/27 genes in asthmatics and 22/27 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, which could impact both acute and chronic effects of cannabis smoke inhalation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".