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. 2017 Feb 14;23(6):999-1009.
doi: 10.3748/wjg.v23.i6.999.

"V体育平台登录" Effect of toll-like receptor 3 agonist poly I:C on intestinal mucosa and epithelial barrier function in mouse models of acute colitis

Hong-Wei Zhao  1 , Yue-Hong Yue  1 , Hua Han  1 , Xiu-Li Chen  1 , Yong-Gang Lu  1 , Ji-Min Zheng  1 , Hong-Tao Hou  1 , Xiao-Meng Lang  1 , Li-Li He  1 , Qi-Lu Hu  1 , Zi-Qian Dun  1
Affiliations

Effect of toll-like receptor 3 agonist poly I:C on intestinal mucosa and epithelial barrier function in mouse models of acute colitis

Hong-Wei Zhao et al. World J Gastroenterol. .

Abstract

Aim: To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis VSports手机版. .

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 libitum for 7 d V体育安卓版. 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. V体育ios版.

Conclusion: 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 VSports最新版本. .

Keywords: Dextran sulfate sodium-induced acute colitis; Epithelial barrier disruption; Mucosal injury; Poly I:C; Tight junction V体育平台登录. .

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Conflict of interest statement (VSports注册入口)

Conflict-of-interest statement: The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effect of poly I:C administration on dextran sulfate sodium-induced acute colitis. A: The percentage of body weight change assessed daily during 1 to 8 d observation; B: Change in the disease activity index that was comprised of body weight loss, stool consistency and occult blood; C: Representative photographs of colon obtained after monitoring clinical development of colitis for 8 d; D: Quantitative analysis of the length of the colon; E: Macroscopic score inflammation assessed; F: Histological scores of the colon tissues; G: Representative photographs of HE staining of colon tissues (Magnifications, × 200). Data are expressed as mean ± SD. bP < 0.01 vs control group; dP < 0.01 vs model group.
Figure 2
Figure 2
Effect of poly I:C on intestinal barrier in dextran sulfate sodium-induced acute colitis. A: MPO activity was measured; B: Quantification of serum FITC-D as a measure of intestinal barrier functions; C: The ultrastructural features of colon under scanning electron microscope. The colon mucosa in the control group was regular without histological lesion. In the model group, the mucosa showed severe loss with obvious histological lesions, including crypt distortion and abscesses. The lesions were significantly ameliorated by poly I:C pretreatment (Upper images: × 500; Lower images: × 2000). Data are expressed as mean ± SD. bP < 0.01 vs control group; dP < 0.01 vs model group. FITC-D: Fluorescein isothiocyanate labeled-dextran; MPO: myeloperoxidase.
Figure 3
Figure 3
Effect of poly I:C on the expressions of inflammatory markers. A: Representative photographs of immunohistochemistry staining of IL-17, TNF-α and IFN-γ in colon tissues (Magnifications, × 200); B: Expressions of IL-17, TNF-α and IFN-γ at the mRNA level, as analyzed by RT-qPCR; C: Protein expressions of IL-17, TNF-α and IFN-γ as analyzed by Western Blot. Data are expressed as mean ± SD. bP < 0.01 vs control group; dP < 0.01 vs model group. RT-qPCR: Real-time quantitative polymerase chain reaction; IL-17: Interleukin-17; TNF-α: Tumor necrosis factor-α; IFN-γ: Interferon-γ.
Figure 4
Figure 4
Effect of poly I:C on colonic epithelial junctions. A: Representative photographs of immunohistochemistry staining for zo-1, occludin and claudin-1 (Magnification: × 200); B: Representative photographs of immunofluorescent staining for zo-1 (green), occludin and claudin-1 (red); C: Expressions of zo-1, occludin and clandin-1 at the mRNA level, as analyzed by RT-qPCR; D: Protein expressions of zo-1, occludin and clandin-1 as analyzed by Western Blot. Data are expressed as mean ± SD. bP < 0.01 vs control group; dP < 0.01 vs model group. RT-qPCR: Real-time quantitative polymerase chain reaction.
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