title: β2 adrenergic agonist attenuates house dust mite-induced allergic airway inflammation through dendritic cells.
abstract: BACKGROUND
  Long-acting β2 adrenergic agonists (LABAs) are commonly used combined with inhaled corticosteroids (ICS) to treat asthmatic patients. Previous reports suggest that LABAs have an anti-inflammatory effect in bronchial asthma, and this should be further investigated. The aim of this study was to investigate whether LABAs inhibit allergic airway inflammation and how this occurs.
  
  
  RESULTS
  We assessed the effect of the LABA formoterol (FORM) on inflammatory cell responses in airway, lung and regional lymph nodes, using an HDM-induced murine allergic asthma model in vivo. The effect of FORM on cytokine production from bone marrow derived dendritic cells (BMDCs) stimulated with HDM was evaluated in vitro. Adoptive transfer of BMDCs pulsed with HDM in the presence or absence of FORM to naïve mice was performed and the inflammatory response to subsequent HDM challenge was analyzed. FORM treatment suppressed HDM-induced changes and caused an increase in the number of eosinophils and neutrophils in bronchoalveolar lavage. The concentration of IL-4 and IL-17 in lung tissue homogenate was elevated and led to an accumulation of IL-4, IL-13, IL-5 and IL-17 producing cells in regional lymph nodes. FORM inhibited the production of IL-6 and IL-23 from BMDCs stimulated with HDM in vitro, and enhanced IL-10 production. The BMDCs adoptive transfer experiment indicated that dendritic cells mediate the effect of FORM, since FORM treatment of BMDCs in vitro attenuated airway inflammation.
  
  
  CONCLUSIONS
  These results suggested that FORM modulates dendritic cell function and attenuates Th2 and Th17 responses induced by HDM. Thus, we propose that the clinical significance of LABAs should be re-investigated taking into account these immune-modulating effects.
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. go.kato.go@gmail.com.
authors.forename: Go
authors.initials: G
authors.lastname: Kato
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. takahak@cc.saga-u.ac.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. tashirohrk@gmail.com.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tashiro
authors.affiliation: Institute of Tokyo Environmental Allergy, 1-2-5, Yushima, Bunkyo-ku, Tokyo, 113-0034, Japan. kurata@itea.jp.
authors.forename: Keigo
authors.initials: K
authors.lastname: Kurata
authors.affiliation: Institute of Tokyo Environmental Allergy, 1-2-5, Yushima, Bunkyo-ku, Tokyo, 113-0034, Japan. shirai@itea.jp.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Shirai
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. shkimu@cc.saga-u.ac.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan. hayashs@cc.saga-u.ac.jp.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hayashi
mesh_terms: D019264:Adoptive Transfer; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D040001:Dermatophagoides farinae; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D000068759:Formoterol Fumarate; D051379:Mice; D008807:Mice, Inbred BALB C; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D016207:Cytokines; D004983:Ethanolamines; D000068759:Formoterol Fumarate