title: Nicotinic acetylcholine receptor stimulation impairs epidermal permeability barrier function and recovery and modulates cornified envelope proteins.
abstract: OBJECTIVE
  To characterize how nicotinic acetylcholine receptors (nAChRs) influence epidermal barrier function and recovery following prolonged stress or direct nAChR activation or antagonism.
  
  
  METHODS
  Mice were subjected to psychological stress or treated topically with nAChR agonist or antagonist for 3 days. We assessed barrier permeability and recovery by measuring transepidermal water loss (TEWL) before and after barrier disruption. In parallel, we analyzed the production and localization of several epidermal cornified envelope proteins in mouse skin and in human EpiDerm™ organotypic constructs stimulated with a nAChR agonist (nicotine) and/or a nAChR selective antagonist (α-bungarotoxin).
  
  
  RESULTS
  We determined that psychological stress in mice impairs barrier permeability function and recovery, an effect that is reversed by application of the α7 selective nAChR antagonist, α-bungarotoxin (Bung). In the absence of stress, both topical nicotine or Bung treatment alone impaired barrier permeability. We further observed that stress, topical nicotine, or topical Bung treatment in mice influenced the abundance and/or localization of filaggrin, loricrin, and involucrin. Similar alterations in these three major cornified envelope proteins were observed in human EpiDerm™ cultures.
  
  
  CONCLUSIONS
  Perceived psychological stress and nicotine usage can both initiate or exacerbate several dermatoses by altering the cutaneous permeability barrier. Modulation of nAChRs by topical agonists or antagonists may be used to improve epidermal barrier function in skin diseases associated with defects in epidermal barrier permeability.
authors.affiliation: Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Curtis
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Plichta
authors.forename: Hanz
authors.initials: H
authors.lastname: Blatt
authors.forename: Steven
authors.initials: S
authors.lastname: Droho
authors.forename: Tina M
authors.initials: TM
authors.lastname: Griffin
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Radek
mesh_terms: D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004817:Epidermis / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D013312:Stress, Physiological
chemical_list: D002038:Bungarotoxins; D018680:Cholinergic Antagonists; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D018722:Nicotinic Agonists; D011498:Protein Precursors; D011978:Receptors, Nicotinic; C064554:loricrin; C032253:involucrin; D009538:Nicotine