Published online Feb 14, 2017. doi: 10.3748/wjg.v23.i6.999
Peer-review started: August 19, 2016
First decision: September 6, 2016
Revised: September 26, 2016
Accepted: October 30, 2016
Article in press: October 31, 2016
Published online: February 14, 2017
To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis.
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 libitum for 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).
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.
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.
Core tip: Poly I:C, a toll-like receptor 3 agonist, has been previously reported to protect against acute colitis. The potential effects of poly I:C on mucosal injury and epithelial barrier disruption were investigated in mouse models of dextran sulfate sodium (DSS)-induced acute colitis. Poly I:C administration dramatically protected against DSS-induced colitis, with ameliorated ultrastructural changes of colon epithelium, intestinal permeability and tight junction protein expressions. Poly I:C may protect against DSS-induced colitis through maintaining integrity of the epithelial barrier and regulating innate immune responses.