PMID- 15306842
OWN - NLM
STAT- MEDLINE
DCOM- 20050216
LR  - 20121115
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 11
IP  - 24
DP  - 2004 Dec
TI  - In vivo transfection of a cis element 'decoy' against signal transducers and 
      activators of transcription 6 (STAT6)-binding site ameliorates IgE-mediated 
      late-phase reaction in an atopic dermatitis mouse model.
PG  - 1753-62
AB  - Signal transducers and activators of transcription 6 (STAT6) play a crucial role 
      in the transactivation of IL-4 and IL-13, which might be involved in the 
      pathogenesis of atopic dermatitis (AD). We herein reported that the IgE-mediated 
      late-phase reaction significantly decreased in STAT6-deficient (STAT6(-/-)) mice 
      in AD model mice induced by intravenous injection of monoclonal 
      anti-dinitrophenyl (DNP)-IgE antibody and subsequent skin testing with 
      dinitrofluorobenzene. We therefore hypothesized that synthetic double-stranded 
      DNA with a high affinity for STAT6 could be introduced in vivo as decoy cis 
      elements to bind the transcriptional factor and block the gene activation 
      contributing to the onset and progression of AD, thus providing effective therapy 
      for AD. Treatment by the transfection of STAT6 decoy oligodeoxynucleotides 
      (ODNs), but not scramble decoy ODN after sensitization by anti-DNP-IgE antibody, 
      had a significant inhibitory effect on not only STAT6 binding to nuclei but also 
      on the late-phase response. A histological analysis revealed that both edema and 
      the infiltration of neutrophils and eosinophils significantly decreased in STAT6 
      decoy ODN-transfected mice. To examine the mechanism of the in vivo effect of 
      STAT6 decoy ODN, we employed an in vitro mast cells culture system. After IgE 
      receptor engagement, mast cells transfected by STAT6 decoy ODN exhibited normal 
      histamine release, but their cytokine release (TNF-alpha, IL-6) markedly 
      decreased. We herein report the first successful in vivo transfer of STAT6 decoy 
      ODN to reduce the late-phase reaction, thereby providing a new therapeutic 
      strategy for AD.
FAU - Yokozeki, H
AU  - Yokozeki H
AD  - Department of Dermatology and Immunodermatology, Graduate School, Tokyo Medical 
      and Dental University, Tokyo, Japan.
FAU - Wu, M-H
AU  - Wu MH
FAU - Sumi, K
AU  - Sumi K
FAU - Awad, S
AU  - Awad S
FAU - Satoh, T
AU  - Satoh T
FAU - Katayama, I
AU  - Katayama I
FAU - Takeda, K
AU  - Takeda K
FAU - Akira, S
AU  - Akira S
FAU - Kaneda, Y
AU  - Kaneda Y
FAU - Nishioka, K
AU  - Nishioka K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Dinitrophenols)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (Stat6 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cells, Cultured
MH  - Dermatitis, Atopic/immunology/pathology/*prevention & control
MH  - Dinitrophenols/immunology
MH  - Disease Models, Animal
MH  - Female
MH  - Genetic Therapy/*methods
MH  - Immunoglobulin E/immunology
MH  - Male
MH  - Mast Cells/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Oligodeoxyribonucleotides/genetics
MH  - STAT6 Transcription Factor
MH  - Signal Transduction
MH  - Th2 Cells/immunology
MH  - Trans-Activators/genetics/*metabolism
MH  - *Transfection
EDAT- 2004/08/13 05:00
MHDA- 2005/02/17 09:00
CRDT- 2004/08/13 05:00
PHST- 2004/08/13 05:00 [pubmed]
PHST- 2005/02/17 09:00 [medline]
PHST- 2004/08/13 05:00 [entrez]
AID - 3302341 [pii]
AID - 10.1038/sj.gt.3302341 [doi]
PST - ppublish
SO  - Gene Ther. 2004 Dec;11(24):1753-62. doi: 10.1038/sj.gt.3302341.