title: Recombinant adeno-associated virus carrying thymosin β4suppresses experimental colitis in mice.
abstract: OBJECTIVE
  To investigate the protective effect of a recombinant adeno-associated virus carrying thymosin β4(AAV-Tβ4) on murine colitisviaintracolonic administration.
  
  
  METHODS
  AAV-Tβ4was prepared and intracolonically used to mediate the secretory expression of Tβ4in mouse colons. Dextran sulfate sodium (DSS) was applied to induce the murine ulcerative colitis, and 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to establish a mouse colitis model resembling Crohn's disease. The disease severity and colon injuries were observed and graded to reveal the effects of AAV-Tβ4on colitis. The activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were determined using biochemical assays. Colonic levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-10 were measured using ELISA, and mucosal epithelial cell apoptosis and proliferation were detected by TUNEL assay and immunochemistry, respectively.
  
  
  RESULTS
  Recombinant AAVs efficiently delivered LacZ and Tβ4into the colonic tissues of the mice, and AAV-Tβ4led to a strong expression of Tβ4in mouse colons. In both the DSS and TNBS colitis models, AAV-Tβ4-treated mice displayed distinctly attenuated colon injuries and reduced apoptosis rate of colonic mucosal epithelia. AAV-Tβ4significantly reduced inflammatory cell infiltrations and relieved oxidative stress in the inflamed colons of the mice, as evidenced by decreases in MPO activity and MDA content and increases in SOD activity. AAV-Tβ4also modulated colonic TNF-α, IL-1β and IL-10 levels and suppressed the compensatory proliferation of colonic epithelial cells in DSS- and TNBS-treated mice.
  
  
  CONCLUSIONS
  Tβ4exerts a protective effect on murine colitis, indicating that AAV-Tβ4could potentially be developed into a promising agent for the therapy of inflammatory bowel diseases.
authors.affiliation: Xiao-Yan Zheng, Qian Li, Zhi-Ming Hao, Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zheng
authors.affiliation: Xiao-Yan Zheng, Qian Li, Zhi-Ming Hao, Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Lv
authors.affiliation: Xiao-Yan Zheng, Qian Li, Zhi-Ming Hao, Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.affiliation: Xiao-Yan Zheng, Qian Li, Zhi-Ming Hao, Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Xiao-Yan Zheng, Qian Li, Zhi-Ming Hao, Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Qian-Nan
authors.initials: QN
authors.lastname: Zhang
authors.affiliation: Xiao-Yan Zheng, Qian Li, Zhi-Ming Hao, Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Xue-Ting
authors.initials: XT
authors.lastname: Zhang
authors.affiliation: Xiao-Yan Zheng, Qian Li, Zhi-Ming Hao, Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Hao
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism*; D003106:Colon / Q000201:enzymology / Q000378:metabolism*; D003424:Crohn Disease / Q000139:chemically induced / Q000378:metabolism*; D004274:DNA, Recombinant / Q000008:administration & dosage; D000229:Dependovirus / Q000235:genetics; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D020895:Enterocytes / Q000378:metabolism / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000008:administration & dosage; D007120:Immunochemistry; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013947:Thymosin / Q000378:metabolism*; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099201:Thymosin beta(4)
chemical_list: D004274:DNA, Recombinant; D016264:Dextran Sulfate; D016753:Interleukin-10; D053583:Interleukin-1beta; D008315:Malondialdehyde; D009195:Peroxidase; D013482:Superoxide Dismutase; D013947:Thymosin; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha; D000099201:Thymosin beta(4); C556062:IL10 protein, mouse; C587672:IL1B protein, mouse
keywords: 2,4,6-trinitrobenzene sulfonic acid; Colitis; Dextran sulfate sodium; Mice; Thymosin β4