title: Functional significance of non-neuronal acetylcholine in skin epithelia.
abstract: In recent years, the physiological role of non-neuronal acetylcholine (ACh) and its receptors (AChR) in epidermal physiology has been under intense investigation. However, little is known about the role of the non-neuronal cholinergic system in inflammatory skin diseases. We chose the clinically nicotine-dependent skin disease hidradenitis suppurativa (HS) as model to study the influence of long term nicotine ingestion on epidermal morphology and AChR expression. HS is a chronic inflammatory, disabling disease of unknown pathogenesis emerging from the pilosebaceous unit of the intertriginous areas. In order to correlate our findings to specific nicotine effects, we used the organotypical coculture system (OTC) and raised artificial epidermis in the presence of nicotine. After 12 days in culture control OTC showed a mature epithelium, while nicotine treated OTCs were significantly thicker. Using immunofluorescence analysis, nicotine treated OTCs produced significantly stronger immunoreactivity (IR) for the alpha3, M(3) and M(5) AChR antisera than control. In contrast, the alpha7 nAChR antiserum showed a slightly reduced IR in the granular layer and the alpha9 nAChR IR retracted to the lower suprabasal layers. In HS epidermis we found the strongest IR for all AChR around the follicular infundibulum while in the sinus epithelia it was only weak. In contrast to the nicotine treated OTC, the alpha7 nAChR IR in the hyperplastic HS epidermis was clearly extended to all living layers. Altogether we provide first hints for a causative role of the non-neuronal cholinergic system in the pathogenesis of HS by promoting infundibular epithelial hyperplasia and thus follicular plugging.
authors.affiliation: Department of Dermatology, Venereology and Allergology, Medical Faculty of Mannheim, Ruprecht-Karls University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68135 Mannheim, Germany.
authors.forename: Anisa
authors.initials: A
authors.lastname: Hana
authors.forename: Dirk
authors.initials: D
authors.lastname: Booken
authors.forename: Carmen
authors.initials: C
authors.lastname: Henrich
authors.forename: Alexei
authors.initials: A
authors.lastname: Gratchev
authors.forename: Nicole
authors.initials: N
authors.lastname: Maas-Szabowski
authors.forename: Sergij
authors.initials: S
authors.lastname: Goerdt
authors.forename: Hjalmar
authors.initials: H
authors.lastname: Kurzen
mesh_terms: D000109:Acetylcholine / Q000378:metabolism* / Q000502:physiology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D017497:Hidradenitis Suppurativa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D009924:Organ Culture Techniques / Q000379:methods; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012907:Smoking / Q000503:physiopathology; D014029:Tobacco Use Disorder / Q000503:physiopathology
chemical_list: D011978:Receptors, Nicotinic; D009538:Nicotine; D000109:Acetylcholine