title: Endocannabinoids regulate growth and survival of human eccrine sweat gland-derived epithelial cells.
abstract: The functional existence of the emerging endocannabinoid system (ECS), one of the new neuroendocrine players in cutaneous biology, is recently described in the human skin. In this study, using human eccrine sweat gland-derived immortalized NCL-SG3 model cells and a wide array of cellular and molecular assays, we investigated the effects of prototypic endocannabinoids (anandamide, 2-arachidonoylglycerol) on cellular functions. We show here that both endocannabinoids dose-dependently suppressed proliferation, induced apoptosis, altered expressions of various cytoskeleton proteins (e.g., cytokeratins), and upregulated lipid synthesis. Interestingly, as revealed by specific agonists and antagonists as well as by RNA interference, neither the metabotropic cannabinoid receptors (CB) nor the "ionotropic" CB transient receptor potential ion channels, expressed by these cells, mediated the cellular actions of the endocannabinoids. However, the endocannabinoids selectively activated the mitogen-activated protein kinase signaling pathway. Finally, other elements of the ECS (i.e., enzymes involved in the synthesis and degradation of endocannabinoids) were also identified on NCL-SG3 cells. These results collectively suggest that cannabinoids exert a profound regulatory role in the biology of the appendage. Therefore, from a therapeutic point of view, upregulation of endocannabinoid levels might help to manage certain sweat gland-derived disorders (e.g., tumors) characterized by unwanted growth.
authors.affiliation: DE-MTA Lendulet Cellular Physiology Research Group, Department of Physiology, University of Debrecen, Research Center for Molecular Medicine, Debrecen, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Czifra
authors.forename: Attila G
authors.initials: AG
authors.lastname: Szöllősi
authors.forename: Balázs I
authors.initials: BI
authors.lastname: Tóth
authors.forename: Julien
authors.initials: J
authors.lastname: Demaude
authors.forename: Charbel
authors.initials: C
authors.lastname: Bouez
authors.forename: Lionel
authors.initials: L
authors.lastname: Breton
authors.forename: Tamás
authors.initials: T
authors.lastname: Bíró
mesh_terms: D001095:Arachidonic Acids / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D003599:Cytoskeleton / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D005989:Glycerides / Q000494:pharmacology; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008954:Models, Biological; D009336:Necrosis; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D034622:RNA Interference; D043882:Receptors, Cannabinoid / Q000378:metabolism; D013545:Sweat Glands / Q000166:cytology* / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D008055:Lipids; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D013778:Tetrazolium Salts; D013844:Thiazoles; C094503:glyceryl 2-arachidonate; C022616:thiazolyl blue; D002118:Calcium; C078814:anandamide