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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zheng, Xiaoyan Lv, Yifei Li, Shuang Zhang, Qiannan Zhang, Xueting Hao, Zhiming |
| Description | Author Affiliation: Zheng X ( Department of Rheumatology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China.); Lv Y ( Department of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi Province, People's Republic of China.); Li S ( Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China.); Zhang Q ( Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China.); Zhang X ( Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China.); Hao Z ( Department of Rheumatology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China. haozhm66@126.com.) |
| Abstract | BACKGROUND: Extracellular high mobility group box 1 (HMGB1) is crucially implicated in the pathogenesis of inflammatory bowel diseases (IBDs). A box domain of HMGB1 has been identified as a specific antagonist of HMGB1. In the present study, we tested the effects of adeno-associated virus (AAV)-mediated colonic secretory expression of HMGB1 A box on murine experimental colitis. METHODS: Self-complementary AAV-2 carrying mouse immunoglobin Gκ leader-human HMGB1 A box (AAV-HMGB1 A box) was constructed. The effects of intracolonically administered AAV-HMGB1 A box on dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis were assessed by the disease activity index (DAI), colon length, macroscopic and histological scoring, myeloperoxidase (MPO) activity, and epithelial apoptosis and complementary proliferation. Colonic immune cell infiltrates, mucosal malondialdehyde content and superoxide dismutase activity, colonic tumor necrosis factor- (TNF- ), interleukin (IL)-1ß and IL-10 levels, serum HMGB1 concentration, and colonic HMGB1 release were determined to investigate the underlying mechanisms. RESULTS: Intracolonically administered AAV-HMGB1 A box efficiently mediated secretory expression of HMGB1 A box and led to significant decreases in DAI, macroscopic and histological scores and colonic epithelial apoptosis in both DSS- and TNBS-treated mice. Modulating inflammation-associated cytokines, such as inhibiting colonic TNF- and IL-1ß expression, decreasing HMGB1 release, and restoring colonic IL-10 levels, and thereby inhibiting inflammatory cell infiltration and alleviating oxidant damage, might be the underlying mechanism. CONCLUSIONS: Intracolonic application of AAV-HMGB1 A box is effective in alleviating murine colitis and has therapeutic potential in human IBDs. |
| File Format | HTM / HTML |
| ISSN | 1099498X |
| Issue Number | 10 |
| Journal | The Journal of Gene Medicine |
| Volume Number | 18 |
| e-ISSN | 15212254 |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2016-10-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Drug Discovery Molecular Biology Molecular Medicine Genetics (clinical) |
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