title: μ-opioid receptor-mediated alterations of allergen-induced immune responses of bronchial lymph node cells in a murine model of stress asthma.
abstract: BACKGROUND
  Psychological stress has a recognized association with asthma symptoms. Using a murine model of allergic asthma, we recently demonstrated the involvement of μ-opioid receptors (MORs) in the central nervous system in the stress-induced exacerbation of airway inflammation. However, the involvement of MORs on neurons and immunological alterations in the stress asthma model remain unclear.
  
  
  METHODS
  MOR-knockout (MORKO) mice that express MORs only on noradrenergic and adrenergic neurons (MORKO/Tg mice) were produced and characterized for stress responses. Sensitized mice inhaled antigen and were then subjected to restraint stress. After a second antigen inhalation, bronchoalveolar lavage cells were counted. Before the second inhalation, bronchial lymph node (BLN) cells and splenocytes from stressed and non-stressed mice were cultured with antigen, and cytokine levels and the proportions of T cell subsets were measured.
  
  
  RESULTS
  Stress-induced worsening of allergic airway inflammation was observed in wild-type and MORKO/Tg mice but not MORKO mice. In wild-type stressed mice, IFN-γ/IL-4 ratios in cell culture supernatants and the proportion of regulatory T cells in BLN cell populations were significantly lower than those in non-stressed mice. These differences in BLN cells were not observed between the stressed and non-stressed MORKO mice. Restraint stress had no effect on cytokine production or T cell subsets in splenocytes.
  
  
  CONCLUSIONS
  Restraint stress aggravated allergic airway inflammation in association with alterations in local immunity characterized by greater Th2-associated cytokine production and a reduced development of regulatory T cells, mediated by MORs.
authors.affiliation: Department of Pathophysiology, Tohoku Pharmaceutical University, Miyagi, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Okuyama
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ide
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sakurada
authors.forename: Kazumasu
authors.initials: K
authors.lastname: Sasaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Gen
authors.initials: G
authors.lastname: Tamura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ohkawara
authors.forename: Motoaki
authors.initials: M
authors.lastname: Takayanagi
authors.forename: Isao
authors.initials: I
authors.lastname: Ohno
mesh_terms: D059331:Adrenergic Neurons / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000523:psychology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000523:psychology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D017450:Receptors, Opioid, mu; D015847:Interleukin-4; D007371:Interferon-gamma