title: Cholinergic anti-inflammatory pathway in the non-obese diabetic mouse model.
abstract: OBJECTIVE
  Activation of the cholinergic anti-inflammatory pathway (CAP) has been shown to reduce inflammation in animal models, while abrogation of the pathway increases inflammation. We investigated whether modulation of CAP influences inflammation in the non-obese diabetic (NOD) mouse model for Sjögren's syndrome and type 1 diabetes.
  
  
  METHODS
  The alpha-7 nicotinic acetylcholine receptor (α7nAChR) was stimulated with AR-R17779 or nicotine in NOD mice. In a second study, unilateral cervical vagotomy was performed. α7nAChR expression, focus scores, and salivary flow were evaluated in salivary glands (SG) and insulitis score in the pancreas. Cytokines were measured in serum and SG.
  
  
  RESULTS
  α7nAChR was expressed on myoepithelial cells in SG. Monocyte chemotactic protein-1 levels were reduced in SG after AR-R17779 treatment and tumor necrosis factor production was increased in the SG of the vagotomy group compared to controls. Focus score and salivary flow were unaffected. NOD mice developed diabetes more rapidly after vagotomy, but at completion of the study there were no statistically significant differences in number of mice that developed diabetes or in insulitis scores.
  
  
  CONCLUSIONS
  Intervention of the CAP in NOD mice leads to minimal changes in inflammatory cytokines, but did not affect overall inflammation and function of SG or development of diabetes.
authors.affiliation: Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology and immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: F A
authors.initials: FA
authors.lastname: Koopman
authors.affiliation: Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology and immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: J L
authors.initials: JL
authors.lastname: Vosters
authors.affiliation: Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology and immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Roescher
authors.affiliation: Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology and immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Broekstra
authors.affiliation: Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology and immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.|University of Cambridge, Cambridge, UK.|Ghent University, Ghent, Belgium.|GlaxoSmithKline, Stevenage, UK.
authors.forename: P P
authors.initials: PP
authors.lastname: Tak
authors.affiliation: Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology and immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Vervoordeldonk
mesh_terms: D000818:Animals; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation; D007515:Islets of Langerhans / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D009538:Nicotine / Q000494:pharmacology; D010195:Pancreatitis / Q000378:metabolism* / Q000473:pathology; D012463:Saliva / Q000378:metabolism; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism*; D012472:Salivation / Q000187:drug effects; D012859:Sjogren's Syndrome / Q000378:metabolism*; D013141:Spiro Compounds / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014628:Vagotomy; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000187:drug effects / Q000378:metabolism*
chemical_list: C408128:AR-R 17779; D001952:Bridged-Ring Compounds; D018932:Chemokine CCL2; D013141:Spiro Compounds; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine
keywords: NOD mouse model; Sjögren's syndrome; acetylcholine; cholinergic anti-inflammatory pathway; diabetes; α7nAChR