title: Therapeutic effect of CpG-enriched plasmid administration on the tight-skin mouse model of scleroderma.
abstract: Immunostimulatory CpG motifs can preferentially induce Th1 immune responses and have been applied to treat Th2-dominant disease. In this study, we investigated whether a plasmid with the addition of 20 copies of an immunostimulatory CpG motif (pB-CpG20) might prevent the development of scleroderma-like syndrome in tight-skin (Tsk/+) mice. Administration of pB-CpG20 to Tsk/+mice every 3 weeks starting at the age of 1 week reduced skin thickness and collagen content compared to that of pB or saline. The reduction was long lasting even after halting the treatment. Furthermore, this treatment partially reduced the production of anti-nuclear antibodies although it did not decrease the incidence of lung emphysema. pB-CpG20 increased the number of spleen cells secreting IFN-gamma and reduced that of the cells secreting IL-4 in vivo and in vitro compared to saline. These results suggest that repeated administration of a CpG-enriched plasmid can ameliorate scleroderma-like syndrome by biasing Th1 immunity in young Tsk/+mice.
authors.affiliation: Department of Immunology, Yokohama City University School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Motohide
authors.initials: M
authors.lastname: Ichino
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Ikejima
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Kojima
authors.forename: Kenji
authors.initials: K
authors.lastname: Okuda
authors.forename: Mutsuhiko
authors.initials: M
authors.lastname: Minami
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020862:GC Rich Sequence / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology