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

Autor: Fantauzzi MF; Firestone Institute for Respiratory Health - Division of Respirology, Dept of Medicine, McMaster University, Hamilton, ON, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada., Aguiar JA; Dept of Biology, University of Waterloo, Waterloo, ON, Canada., Tremblay BJ; Dept of Biology, University of Waterloo, Waterloo, ON, Canada., Mansfield MJ; Genomics and Regulatory Systems Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Japan., Yanagihara T; Firestone Institute for Respiratory Health - Division of Respirology, Dept of Medicine, McMaster University, Hamilton, ON, Canada., Chandiramohan A; Firestone Institute for Respiratory Health - Division of Respirology, Dept of Medicine, McMaster University, Hamilton, ON, Canada., Revill S; Firestone Institute for Respiratory Health - Division of Respirology, Dept of Medicine, McMaster University, Hamilton, ON, Canada., Ryu MH; Division of Respiratory Medicine, Dept of Medicine, University of British Columbia, Vancouver, BC, Canada., Carlsten C; Division of Respiratory Medicine, Dept of Medicine, University of British Columbia, Vancouver, BC, Canada., Ask K; Firestone Institute for Respiratory Health - Division of Respirology, Dept of Medicine, McMaster University, Hamilton, ON, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada., Stämpfli M; Firestone Institute for Respiratory Health - Division of Respirology, Dept of Medicine, McMaster University, Hamilton, ON, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada., Doxey AC; Firestone Institute for Respiratory Health - Division of Respirology, Dept of Medicine, McMaster University, Hamilton, ON, Canada.; Dept of Biology, University of Waterloo, Waterloo, ON, Canada., Hirota JA; Firestone Institute for Respiratory Health - Division of Respirology, Dept of Medicine, McMaster University, Hamilton, ON, Canada.; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.; Dept of Biology, University of Waterloo, Waterloo, ON, Canada.; Division of Respiratory Medicine, Dept of Medicine, University of British Columbia, Vancouver, BC, Canada.
Jazyk: angličtina
Zdroj: ERJ open research [ERJ Open Res] 2020 Dec 14; Vol. 6 (4). Date of Electronic Publication: 2020 Dec 14 (Print Publication: 2020).
DOI: 10.1183/23120541.00128-2020
Abstrakt: 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. CB 1 , CB 2 , 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 of 32 genes. In contrast, disease status was associated with differential expression of 21 of 32 genes in people with asthma and 26 of 32 genes in people with COPD. We confirm at the protein level that TRPV1, the most differentially expressed candidate in our analyses, was upregulated in airway epithelial cells from people with asthma relative to healthy subjects. Our data demonstrate that the 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.
Competing Interests: Conflict of interest: M.F. Fantauzzi has nothing to disclose. Conflict of interest: J.A. Aguiar has nothing to disclose. Conflict of interest: B.J-M. Tremblay has nothing to disclose. Conflict of interest: M.J. Mansfield has nothing to disclose. Conflict of interest: T. Yanagihara has nothing to disclose. Conflict of interest: A. Chandiramohan has nothing to disclose. Conflict of interest: S. Revill has nothing to disclose. Conflict of interest: M. Hyung Ryu has nothing to disclose. Conflict of interest: C. Carlsten has nothing to disclose. Conflict of interest: K. Ask has nothing to disclose. Conflict of interest: M. Stämpfli has nothing to disclose. Conflict of interest: A.C. Doxey has nothing to disclose. Conflict of interest: J.A. Hirota has nothing to disclose.
(Copyright ©ERS 2020.)
Databáze: MEDLINE