| 1 | Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice显示文摘AIM: To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium(DSS)-induced acute colitis.METHODS: Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence(NIRF) imaging following intradermal injection of indocyanine green(ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSSadministration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin(BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest(ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. RESULTS: Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired uptake of a lipid tracer within mesenteric lymphatics. Our in vivo NIRF imaging data demonstrated dilated dermal lymphatic vessels, which were confirmed by immunohistochemical staining of lymphatic vessels, and significantly reduced lymphatic contractile function in the skin of mice with DSS-induced acute colitis. Quantification of the fluorescent intensity remaining in the depot as a function of time showed that there was significantly higher Alexa680-BSA fluorescence in mice with DSSinduced acute colitis compared to pre-treatment with DSS, indicative of impaired lymphatic drainage.CONCLUSION: The lymphatics are locally and systemically altered in acute colitis, and functional NIRF imaging is useful for noninvasively monitoring systemic lymphatic changes during inflammation. | Germaine D Agollah Grace Wu Ho-Lan Peng Sunkuk Kwon | 2015 | World Journal of Gastroenterology2015，21，45： | 2 |
| 2 | Intestinal ischemia-reperfusion of macaques triggers a strong innate immune response显示文摘AIM:To investigate inflammatory injury in the intestinal mucosa after intestinal ischemia-reperfusion(ⅡR) with Toll-like receptor(TLR)-mediated innate immunity.METHODS:Ten macaques were randomized into control and ⅡR groups.The distribution and expression level of TLR2,TLR4,MD2,nuclear factor(NF)-κB p65 and interferon(IFN)-γ were measured by immunohistochemical stain and western blotting.The mRNA expression of TLR4,TLR2,MD2,interleukin(IL)-1β and tumor necrosis factor(TNF)-α were measured by reverse transcriptase-polymerase chain reaction.The cytokine levels in blood and intestinal tissues were measured by ELISA.RESULTS:Obvious hemorrhage and erosion of mucosae were seen in the ⅡR group.Expression of TLR2,TLR4,MD2,NF-κB p65 and IFN-γ was significantly higher in the ⅡR group than in the control group(0.13 ± 0.04,0.22 ± 0.04,0.16 ± 0.06,0.65 ± 0.12,0.38 ± 0.10 vs 0.07 ± 0.04,0.08 ± 0.03,0.04 ± 0.02,0.19 ± 0.06,0.14 ± 0.05,P < 0.05).In addition,the expression of TLR2,TLR4,MD2,IL-1β and TNF-α mRNA in the ⅡR group were significantly higher than those of control group(1.52 ± 0.15,1.39 ± 0.06,1.94 ± 0.12,1.48 ± 0.15,0.66 ± 0.08 vs 0.31 ± 0.05,0.5 ± 0.04,0.77 ± 0.05,0.35 ± 0.08,0.18 ± 0.04,P < 0.05).Furthermore,IL-1β,IL-6 and TNF-α levels in the macaques ileum and plasma were significantly higher than in the control group(plasma:86.3 ± 15.2,1129 ± 248.3,77.8 ± 16.2 vs 29.5 ± 7.3,19.8 ± 8.2,5.6 ± 1.7; ileum:273.4.± 44.7,1636 ± 168.0,205.5 ± 30.7 vs 76.8 ± 20.5,663.4 ± 186.9,49.0 ± 9.4; P < 0.05).CONCLUSION:After ⅡR,general inflammatory injury in the intestinal mucosa is correlated with a strong innate immune response,mediated by activation of the TLR-NF-κB-cytokine pathway. | Hao Wu Yi-Yun Deng Ling Liu Qing-Hua Tan Chun-Hui Wang Mei-Mei Guo Yong-Mei Xie Cheng-Wei Tang | 2014 | World Journal of Gastroenterology2014，20，41： | 1 |
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