title: Amelioration of murine dextran sulfate sodium-induced colitis by ex vivo extracellular superoxide dismutase gene transfer.
abstract: BACKGROUND
  Although the etiology of inflammatory bowel disease has not been fully clarified, reactive oxygen species is speculated to be involved. Extracellular superoxide dismutase (EC-SOD), an isozyme of SODs, is known to function mainly in body fluids. We investigated the efficacy of an ex vivo EC-SOD gene transfer into dextran sulfate sodium (DSS)-induced colitis mice.
  
  
  METHODS
  Experimental colitis was induced by providing Balb/c mice with DSS in sterile distilled water provided as desired. The syngenic fibroblasts were obtained from Balb/c mice embryos and retrovirally transduced with the hEC-SOD gene. These engineered cells were confirmed to secrete EC-SOD in culture medium by enzyme-linked immunosorbent assay and were inoculated subcutaneously in the backs of DSS-treated mice. Mucosal injury of the colon was evaluated by the disease activity index (DAI: body weight, rectal bleeding, and stool consistency), grading of histologic disease severity, and levels of cytokine (tumor necrosis factor-alpha, interleukin-1beta) production. 8-Hydroxydeoxyguanosine (8-OHdG) levels in the mucosal tissue were assessed by immunohistochemical staining. Malondialdehyde (MDA) was measured using a colorimetric assay.
  
  
  RESULTS
  A significant improvement was observed in DAI score and histologic severity as well as in mucosal tissue levels of inflammatory cytokines, 8-OHdG, and MDA of mice treated with the EC-SOD gene as compared with those without gene therapy, not only in a mild colitis model but also in a severe colitis model. Survival of treated mice in these models was significantly prolonged.
  
  
  CONCLUSIONS
  Ex vivo transfer of the EC-SOD gene was feasible for treatment of DSS-induced colitis.
authors.affiliation: Department of Internal Medicine (Section 4), Sapporo Medical University, School of Medicine, Sapporo, Japan.
authors.forename: Takatomi
authors.initials: T
authors.lastname: Oku
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iyama
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sato
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.forename: Maki
authors.initials: M
authors.lastname: Tanaka
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sagawa
authors.forename: Kageaki
authors.initials: K
authors.lastname: Kuribayashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sumiyosi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Murase
authors.forename: Takuro
authors.initials: T
authors.lastname: Machida
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Okamoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takayama
authors.forename: Minoru
authors.initials: M
authors.lastname: Takahashi
authors.forename: Junji
authors.initials: J
authors.lastname: Kato
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hamada
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Niitsu
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced* / Q000628:therapy*; D003470:Culture Media / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007150:Immunohistochemistry; D007249:Inflammation; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D000925:Anticoagulants; D003470:Culture Media; D016207:Cytokines; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D016264:Dextran Sulfate; D013482:Superoxide Dismutase