Gadolinium chloride improves the course of TNBS and DSS-induced colitis through protecting against colonic mucosal inflammation.
Gadolinium chloride improves the course of TNBS and DSS-induced colitis through protecting against colonic mucosal inflammation.
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氯化钆通过预防结肠粘膜炎症来改善 TNBS 和 DSS 诱导的结肠炎的病程
DOI：
10.1038/srep06096
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发表时间：
2014-08-22
影响因子：
4.6
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Du C;Wang P;Yu Y;Chen F;Liu J;Li Y
结肠粘膜中的炎性巨噬细胞是与炎性肠病（IBD）相关的病理学的主要驱动因素。本文研究了巨噬细胞选择性抑制剂氯化钆（GdCl 3）是否能改善2，4，6-三硝基苯磺酸（TNBS）和葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的病程，并探讨了其可能的机制。通过静脉或直肠途径给予GdCl 3给结肠炎小鼠，我们发现GdCl 3显著改善结肠炎的严重程度，包括体重减轻，疾病活动指数评分降低和粘膜损伤改善。为了探讨其可能的机制，采用流式细胞术检测结肠粘膜巨噬细胞的比例。结果表明，GdCl 3对结肠粘膜巨噬细胞无明显的清除作用，但能显著抑制TNBS和DSS诱导的TNFα、IL-1β和IL-6的分泌。Western blotting结果显示，GdCl 3处理后，结肠炎小鼠结肠黏膜NF-κB p65表达明显减弱。在LPS刺激的RAW 264. 7细胞中证实了GdCl 3的抗炎活性，GdCl 3可能通过抑制NF-κB信号通路下调巨噬细胞产生促炎细胞因子。因此，粘膜炎性巨噬细胞的干预可能是IBD的一个有前途的治疗靶点。
Inflammatory macrophages in colonic mucosa are the leading drivers of the pathology associated with inflammatory bowel disease (IBD). Here we examined whether gadolinium chloride (GdCl3), a macrophage selective inhibitor, would improve the course of 2,4,6-trinitro benzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS)-induced colitis in mice and the potential mechanisms were investigated. By giving GdCl3to colitis mice through intravenous or intrarectal route, we found that GdCl3markedly ameliorated the colitis severity, including less weight loss, decreased disease activity index scores and improved mucosal damage. To investigate the potential mechanisms, flow-cytometric analysis was performed to detect the proportion of mucosal macrophages in colon. The results showed that GdCl3had no macrophage depletion effect in colonic mucosa, but significantly suppressed TNBS and DSS-induced TNFα, IL-1β and IL-6 secretions. Also, Western blotting analysis indicated that NF-κB p65 expression was significantly attenuated in the mucosa in colitis mice with GdCl3treatment. Then, the anti-inflammatory activity of GdCl3was confirmed in LPS-stimulated RAW 264.7 cells that GdCl3might down-regulate the production of proinflammatory cytokines by macrophages through inhibition of the NF-κB signaling pathway. Therefore, intervention with mucosal inflammatory macrophages may be a promising therapeutic target in IBD.
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影响因子：
2.4
作者：
Zhang, Shiwei;Liu, Xuelai;Wong, Kenneth K. Y.
通讯作者：
Wong, Kenneth K. Y.
影响因子：
14.8
作者：
Wirtz, Stefan;Neufert, Clemens;Neurath, Markus F.
通讯作者：
Neurath, Markus F.
影响因子：
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作者：
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Cohen, Donald A.
钆促进的磷酸钙沉淀与 RAW 264.7 巨噬细胞的促纤维化激活有关
影响因子：
3.2
作者：
Gou, Bao-Di;Bian, Sha;Wang, Kui
通讯作者：
Wang, Kui
影响因子：
5.4
作者：
Bain, Calum C.;Mowat, Allan McI
通讯作者：
Mowat, Allan McI