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Immunological approach for the molecular mechanism ofintestinal motility functions

肠蠕动功能分子机制的免疫学方法

基本信息

批准号：
16208029
负责人：
OZAKI Hiroshi
金额：
$ 31.87万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16208029/
关键词：
gut motility smooth muscle macrophage nerve interstitial cell of Caial inflammatory bowel disease cytokines 消化管運動平滑筋収縮常在型マクロファージ IBD 神経機能 ICC 肥満細胞

项目摘要

In this study, we investigated an possible involvement of macrophages and immune cells in intestinal motility disorders by using several IBD models. Detailed findings are as follows;1) In clinical IBD, many mast cells are identified in muscularis. We analyzed a mechanism of mast cell degranulation especially focusing on microfilaments in the cells. Am J Physiol 286: C256-C263, 2004; J Immunology 174:4584-4589, 20052) We first found that PAR-2 was down regulated in DSS-induced colitis model, indicating that relaxing mechanism is also deregulated in IBD. Br J Pharmacol 148 : 200-2007, 20063) We found that ICC networks were destroyed in the artificial intestinal obstruction model in rat. Neurogastroenterology Motility 18, 53-61, 20064) We also found the ICC disorder in intestinal ischemia-reperfusion model mice. J Surgical Research 135 : 255-261, 20065) We identified an importance of TNF-a in the muscularis inflammation in gut using TNF-a deficient mice. This finding was picked up in the … More Editorial Comment. Neurogastroenterology Motility 18, 578-588, 20066) In the TNBS colitis mode, the destroyed ICC network was found to be quickly recovered after the cessation of inflammation. Neurogastroenterology Motility 18, 1019-1030, 20067) As well as Crohn's disease model, CPI-17 was found to be down regulated in ulcerative colitis model. Neurogastroenterology Motility 19, 504-514, 20078) Using histochemical technique, we identified that ICC and also nerve networks were destroyed in the TNBS induced colitis model. Histochem Cell Biol 127 : 41-53, 20079) The down regulation of CPI-17 induced by IL-1β was found to be mediated by the secondary production of TNFα using TNFα and IL-1α/β knockout mice. Am J Physiol 292: G1429-G1438, 200710) We found that IL-1β acts as an anti-proliferative mediator, which acts indirectly through the production of PGE2 and NO from resident macrophage within Real smooth muscle tissue. Am J Physiol 292 : G1315-G1322, 200711) Other studies revealed an involvement of the change in vascular activity in the inflammatory reactions. Am J Resp Crit Care Med 170 : 647-655, 2004; Arteriosclerosis Thrombosis Vascular Biology 25; 1796-1803, 2005; Arteriosclerosis Thrombosis Vascular Biology 25; 1-7, 2005; Eur J Pharmacol 515, 134-141, 2005 etc.Overall, we provided strong evidence for an importance of muscularis inflammation in IBD. Less

在这项研究中，我们调查了可能涉及的巨噬细胞和免疫细胞在肠道动力障碍，通过使用几种IBD模型。具体发现如下：1）在临床IBD中，在肌层中鉴定出许多肥大细胞。我们分析了肥大细胞脱颗粒的机制，特别是关注细胞中的微丝。第286章：一个人C256-C263，2004; J Immunology 174：4584-4589，20052）我们首先发现PAR-2在DSS诱导的结肠炎模型中下调，表明松弛机制在IBD中也被失调。BrJ Pharmacol 148：200-2007，20063）我们发现在大鼠人工肠梗阻模型中ICC网络被破坏。Neurogastroenterology Motility 18，53-61，20064）我们还在肠缺血-再灌注模型小鼠中发现了ICC障碍。J Surgical Research 135：255-261，20065）我们使用TNF-α缺陷小鼠鉴定了TNF-α在肠肌层炎症中的重要性。这一发现是在 ...更多信息编辑评论。Neurogastroenterology Motility 18，578-588，20066）在TNBS结肠炎模式中，发现被破坏的ICC网络在炎症停止后快速恢复。Neurogastroenterology Motility 18，1019-1030，20067）与克罗恩病模型一样，发现CPI-17在溃疡性结肠炎模型中下调。Neurogastroenterology Motility 19，504-514，20078）使用组织化学技术，我们鉴定了ICC以及神经网络在TNBS诱导的结肠炎模型中被破坏。Histochem Cell Biol 127：41-53，20079）发现由IL-1β诱导的CPI-17的下调是由使用TNFα和IL-1α/β敲除小鼠的TNFα的次级产生介导的。第292章：一个人G1429-G1438，2007 10）我们发现IL-1β作为抗增殖介质，其通过从真实的平滑肌组织内的驻留巨噬细胞产生PGE 2和NO间接起作用。Am J Physiol 292：G1315-G1322，2007 - 11）其他研究揭示了炎症反应中血管活性变化的参与。Am J Resp Crit Care Med 170：647-655，2004; Arteriorrhythmia Thrombosis Vascular Biology 25; 1796-1803，2005; Arteriorrhythmia Thrombosis Vascular Biology 25; 1-7，2005; Eur J Pharmacol 515，134-141，2005等。总之，我们提供了肌层炎症在IBD中重要性的有力证据。少