Dextran sodium sulfate (DSS) induces colitis in mice by forming nano-lipocomplexes with medium-chain-length fatty acids in the colon.
Dextran sodium sulfate (DSS) induces colitis in mice by forming nano-lipocomplexes with medium-chain-length fatty acids in the colon.
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DOI：
10.1371/journal.pone.0032084
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Merlin D
中科院分区：
文献类型：
--
作者：
Laroui H;Ingersoll SA;Liu HC;Baker MT;Ayyadurai S;Charania MA;Laroui F;Yan Y;Sitaraman SV;Merlin D
炎症性肠病(IBD)是由多种因素引起的炎症性疾病，主要为溃疡性结肠炎和克罗恩病。对IBD的研究多采用葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎模型。DSS可在体内诱导肠道炎症，但不能在体外诱导肠道炎症。此外，DSS相关分子(游离葡萄糖、硫酸钠溶液、游离葡聚糖)在体外或体内均不会引起肠道炎症。我们发现DSS而不是葡聚糖相关分子与存在于结肠腔中的中链脂肪酸(MCFA)建立了联系，如十二酸。DSS与MCFA络合形成直径为200 nm的纳米囊泡∼，可与结肠细胞膜融合。纳米DSS/MCFA囊泡进入细胞质可能激活肠道炎症信号通路。我们还表明DSS的炎症活性是由右旋糖苷部分介导的。DSS的有害作用主要局限于远端结肠，因此对DSS进行化学修饰以开发对结肠有益的物质而不影响结肠靶向特异性将是非常重要的。
Inflammatory bowel diseases (IBDs), primarily ulcerative colitis and Crohn's disease, are inflammatory disorders caused by multiple factors. Research on IBD has often used the dextran sodium sulfate (DSS)-induced colitis mouse model. DSS induces in vivo but not in vitro intestinal inflammation. In addition, no DSS-associated molecule (free glucose, sodium sulfate solution, free dextran) induces in vitro or in vivo intestinal inflammation. We find that DSS but not dextran associated molecules established linkages with medium-chain-length fatty acids (MCFAs), such as dodecanoate, that are present in the colonic lumen. DSS complexed to MCFAs forms nanometer-sized vesicles ∼200 nm in diameter that can fuse with colonocyte membranes. The arrival of nanometer-sized DSS/MCFA vesicles in the cytoplasm may activate intestinal inflammatory signaling pathways. We also show that the inflammatory activity of DSS is mediated by the dextran moieties. The deleterious effect of DSS is localized principally in the distal colon, therefore it will be important to chemically modify DSS to develop materials beneficial to the colon without affecting colon-targeting specificity.
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影响因子：
14
作者：
Laroui, Hamed;Theiss, Arianne L.;Yan, Yutao;Dalmasso, Guillaume;Nguyen, Hang T. T.;Sitaraman, Shanthi V.;Merlin, Didier
通讯作者：
Merlin, Didier
DOI：
10.2174/1745017901107010051
发表时间：
2011-03-04
期刊：
Clinical practice and epidemiology in mental health : CP & EMH
影响因子：
--
作者：
G, Riva;B K, Wiederhold;A, Gaggioli
通讯作者：
A, Gaggioli
DOI：
10.1111/j.1440-1746.2010.06332.x
发表时间：
2010-11-01
影响因子：
4.1
作者：
Kim, In-Wha;Myung, Seung-Jae;Kim, Jin-Ho
通讯作者：
Kim, Jin-Ho
影响因子：
8.3
作者：
Pinho, RA;Silveira, PCL;Moreira, JCF
通讯作者：
Moreira, JCF
DOI：
10.1152/ajpgi.00262.2004
发表时间：
2005-02-01
影响因子：
4.5
作者：
Charrier, L;Yan, YT;Merlin, D
通讯作者：
Merlin, D