title: Effect of toll-like receptor 3 agonist poly I:C on intestinal mucosa and epithelial barrier function in mouse models of acute colitis.
abstract: OBJECTIVE
  To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis.
  
  
  METHODS
  Thirty C57BL/6 mice were given either regular drinking water (control group) or 2% (w/v) DSS drinking water (model and poly I:C groups)ad libitumfor 7 d. Poly I:C was administrated subcutaneously (20 μg/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin 17 (IL-17) and interferon-γ (IFN-γ). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeled-dextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction (TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction (RT-qPCR).
  
  
  RESULTS
  DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The mRNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-qPCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-α, IL-17 and IFN-γ.
  
  
  CONCLUSIONS
  Our study suggested that poly I:C may protect against DSS-induced colitis through maintaining integrity of the epithelial barrier and regulating innate immune responses, which may shed light on the therapeutic potential of poly I:C in human colitis.
authors.affiliation: Hong-Wei Zhao, Ji-Min Zheng, Hong-Tao Hou, Department of Gastroenterology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Zhao
authors.affiliation: Hong-Wei Zhao, Ji-Min Zheng, Hong-Tao Hou, Department of Gastroenterology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Yue-Hong
authors.initials: YH
authors.lastname: Yue
authors.affiliation: Hong-Wei Zhao, Ji-Min Zheng, Hong-Tao Hou, Department of Gastroenterology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Han
authors.affiliation: Hong-Wei Zhao, Ji-Min Zheng, Hong-Tao Hou, Department of Gastroenterology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Hong-Wei Zhao, Ji-Min Zheng, Hong-Tao Hou, Department of Gastroenterology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Lu
authors.affiliation: Hong-Wei Zhao, Ji-Min Zheng, Hong-Tao Hou, Department of Gastroenterology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Zheng
authors.affiliation: Hong-Wei Zhao, Ji-Min Zheng, Hong-Tao Hou, Department of Gastroenterology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Hou
authors.affiliation: Hong-Wei Zhao, Ji-Min Zheng, Hong-Tao Hou, Department of Gastroenterology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Lang
authors.affiliation: Hong-Wei Zhao, Ji-Min Zheng, Hong-Tao Hou, Department of Gastroenterology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: He
authors.affiliation: Hong-Wei Zhao, Ji-Min Zheng, Hong-Tao Hou, Department of Gastroenterology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Qi-Lu
authors.initials: QL
authors.lastname: Hu
authors.affiliation: Hong-Wei Zhao, Ji-Min Zheng, Hong-Tao Hou, Department of Gastroenterology, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Zi-Qian
authors.initials: ZQ
authors.lastname: Dun
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D007113:Immunity, Innate / Q000187:drug effects; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D010539:Permeability / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D011070:Poly I-C / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D062725:Tight Junction Proteins / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000819:agonists*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D016207:Cytokines; C519703:TLR3 protein, mouse; D062725:Tight Junction Proteins; D051196:Toll-Like Receptor 3; D016264:Dextran Sulfate; D009195:Peroxidase; D011070:Poly I-C
keywords: Dextran sulfate sodium-induced acute colitis; Epithelial barrier disruption; Mucosal injury; Poly I:C; Tight junction