title: Expression and regulation of intercellular adhesion molecule-1 on airway parasympathetic nerves.
abstract: BACKGROUND
  Eosinophils cluster along airway nerves in patients with asthma and release eosinophil major basic protein, an antagonist of inhibitory M2 muscarinic receptors on nerves. Blocking M2 function increases bronchoconstriction, leading to airway hyperreactivity. Intercellular adhesion molecule-1 (ICAM-1) mediates eosinophil adhesion to nerves.
  
  
  OBJECTIVE
  We investigated mechanisms of ICAM-1 expression by parasympathetic nerves.
  
  
  METHODS
  ICAM-1 expression was examined by immunocytochemistry of lung sections from ovalbumin-sensitized and challenged guinea pigs. ICAM-1 was measured in parasympathetic nerves isolated from subjects and guinea pigs and in human neuroblastoma cells by real-time RT-PCR, immunocytochemistry, and Western blot.
  
  
  RESULTS
  ICAM-1 was not detected in control airway parasympatheric nerves in vivo or in cultured cells. ICAM-1 was expressed throughout antigen-challenged guinea pig lung tissue and was selectively decreased by dexamethasone only in nerves. ICAM-1 was induced in human and guinea pig parasympathetic nerves by TNF-alpha and IFN-gamma and was inhibited by dexamethasone and by an inhibitor of nuclear factor-kappaB (NF-kappaB). In neuroblastoma cell lines TNF-alpha and IFN-gamma-induced ICAM-1 was blocked by an inhibitor of NF-kappaB but not by inhibitors of mitogen-activated protein kinases. Dexamethasone did not inhibit ICAM-1 expression in neuroblastoma cells.
  
  
  CONCLUSIONS
  ICAM-1 induced in nerves by antigen challenge and proinflammatory cytokines is sensitive to dexamethasone. ICAM-1 expression is also sensitive to inhibitors of NF-kappaB. Neuroblastoma cells mimic many, but not all, characteristics of ICAM-1 expression in parasympathetic nerves.
  
  
  CONCLUSIONS
  Dexamethasone and NF-kappaB inhibitors could prevent eosinophils from adhering to nerves by blocking ICAM-1 expression on parasympathetic nerves, thus protecting inhibitory M2 muscarinic receptors and making this pathway a potential target for asthma treatment.
authors.affiliation: Division of Physiology and Pharmacology, Oregon Health & Science University, Portland, Ore., USA.
authors.forename: Zhenying
authors.initials: Z
authors.lastname: Nie
authors.forename: Cole S
authors.initials: CS
authors.lastname: Nelson
authors.forename: David B
authors.initials: DB
authors.lastname: Jacoby
authors.forename: Allison D
authors.initials: AD
authors.lastname: Fryer
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000294:innervation* / Q000378:metabolism; D009474:Neurons / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D010047:Ovalbumin