title: Nicotinic acetylcholine receptor expression and susceptibility to cholinergic immunomodulation in human monocytes of smoking individuals.
abstract: OBJECTIVE
  Smoking is generally accepted as a factor that affects the disease course in inflammatory bowel disease patients. Whether these effects can be contributed to the immunomodulatory effects of nicotine via nicotinic acetylcholine receptor (nAChR) activation is unclear. As previous data suggest that the α7 nicotinic acetylcholine receptor (CHRNA7) and its duplicated variant CHRFAM7A may specifically participate in the inflammatory response of monocytes, we evaluated whether repeated nicotine exposure or smoking affects monocyte CHRNA7 and CHRFAM7A expression and cholinergic immunomodulation.
  
  
  METHODS
  The human monocyte cell line THP-I was incubated with nicotine for different time points before endotoxin exposure. In a pilot volunteer study using smoking (n = 4) and nonsmoking (n = 7) individuals, vagal output was stimulated by olive oil administration after which monocytes were analyzed for nicotinic receptor expression. Serum tumor necrosis factor (TNF) levels were determined using ELISA and expression levels of the nAChR subunits CHRNA7, CHRNB2 or CHRFAM7A were analyzed using QPCR.
  
  
  RESULTS
  Repeated nicotine exposure upregulated CHRNA7 expression on THP-I monocytes and led to an enhanced potential of α7 nAChR agonist GSK1345038A to reduce TNF levels. Furthermore, CHRNA7 was only detectable in isolated blood monocytes of smokers. On the other hand, the expression of CHRFAM7A and CHRNB2 was not affected by nicotine exposure. Lipopolysaccharides-induced TNF secretion was inhibited by nicotinic receptor activation in THP-I monocytes, but this response was not consistently seen in blood monocytes from smoking individuals.
  
  
  CONCLUSIONS
  We conclude that CHRNA7 expression on blood monocytes is upregulated in smoking individuals, which may contribute to cholinergic immunomodulation.
authors.affiliation: Tytgat Institute for GI and Liver Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Esmerij P
authors.initials: EP
authors.lastname: van der Zanden
authors.forename: Francisca W
authors.initials: FW
authors.lastname: Hilbers
authors.forename: Caroline
authors.initials: C
authors.lastname: Verseijden
authors.forename: Rene M
authors.initials: RM
authors.lastname: van den Wijngaard
authors.forename: Mike
authors.initials: M
authors.lastname: Skynner
authors.forename: Kevin
authors.initials: K
authors.lastname: Lee
authors.forename: Luis
authors.initials: L
authors.lastname: Ulloa
authors.forename: Guy E
authors.initials: GE
authors.lastname: Boeckxstaens
authors.forename: Wouter J
authors.initials: WJ
authors.lastname: de Jonge
mesh_terms: D000328:Adult; D002460:Cell Line; D005260:Female; D005731:Ganglionic Stimulants / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009538:Nicotine / Q000276:immunology / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D012907:Smoking / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D005731:Ganglionic Stimulants; D009538:Nicotine; D011978:Receptors, Nicotinic; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human