μ-opioid receptor-mediated alterations of allergen-induced immune responses of bronchial lymph node cells in a murine model of stress asthma

Kaori Okuyama, Soichiro Ide, Shinobu Sakurada, Kazumasu Sasaki, Ichiro Sora, Gen Tamura, Yuichi Ohkawara, Motoaki Takayanagi, Isao Ohno

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)245-258
Number of pages14
JournalAllergology International
Volume61
Issue number2
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • Adaptive immune response
  • Allergic asthma
  • Mu opioid receptor
  • Murine model
  • Psychological stress

ASJC Scopus subject areas

  • Immunology and Allergy

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