title: Novel ribbon-type nuclear factor of activated T cells decoy oligodeoxynucleotides preclude airways hyperreactivity and Th2 cytokine expression in experimental asthma.
abstract: BACKGROUND
  Nuclear factor of activated T cells (NFAT) is required for the differentiation of Th2 responses, so we examined its role in mouse experimental asthma and tested the hypothesis that an NFAT blockade with a decoy against NFAT can prevent asthma progression.
  
  
  OBJECTIVE
  To determine the effects of the NFAT decoy oligodeoxynucleotides (ODNs) on the development of airway inflammation, we designed a novel ribbon-type ODN containing two binding sites for NFAT in a single decoy molecule without an open end, which is more stable than a conventional decoy, and largely preserved its structural integrity in the presence of nucleases.
  
  
  METHODS
  Ribbon-type NFAT decoy ODNs were transfected into ovalbumin (OVA)-sensitized CD3+ T cells in vitro. OVA-immunized mice received these cells by intraperitoneal injection. Airway hyperreactivity (AHR) was measured and the transfected CD3+ T cells' responses to the airways were characterized.
  
  
  RESULTS
  Development of AHR after OVA challenge was effectively abolished after adoptive transfer of ribbon-type NFAT decoy ODN transfected CD3+ T cells. Transfer of ribbon-type decoy significantly reduced the number of inflammatory cells and the concentrations of IL-4, IL-5 and IL-13, but not IFN-γ, in the bronchoalveolar lavage of the recipient mice.
  
  
  CONCLUSIONS
  These results suggest the inhibitory effect of ribbon-type decoy ODNs against NFAT on the induction of bronchial asthma. Adoptively transferred CD3+ T cells, which are transfected with NFAT decoy, may be an effective strategy for the treatment of asthma.
authors.affiliation: Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan. ICB75097@nifty.com
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nagashima
authors.forename: Masachika
authors.initials: M
authors.lastname: Akiyama
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sato
authors.forename: Takayuki
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Sasaki
authors.forename: Hiroo
authors.initials: H
authors.lastname: Nitanai
authors.forename: Koko
authors.initials: K
authors.lastname: Kowata
authors.forename: Toshihide
authors.initials: T
authors.lastname: Nakadate
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Uesugi
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sugai
authors.forename: Terutaka
authors.initials: T
authors.lastname: Kakiuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamauchi
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000276:immunology; D017252:CD3 Complex / Q000096:biosynthesis; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D050778:NFATC Transcription Factors / Q000235:genetics; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D018836:Inflammation Mediators; D050778:NFATC Transcription Factors; D020319:Oligodeoxyribonucleotides, Antisense