Immunological approach for the molecular mechanism ofintestinal motility functions

在这项研究中，我们通过几种IBD模型研究了巨噬细胞和免疫细胞在肠道运动障碍中的可能参与。具体表现如下：1)临床IBD患者肌层内可见大量肥大细胞。我们分析了肥大细胞脱颗粒的机制，特别是细胞中的微丝。我们首次发现在DSS诱导的结肠炎模型中PAR-2表达下调，表明松弛机制在IBD中也被破坏。BR J Pharmacol148：200-2007,20063)我们发现在大鼠人工肠梗阻模型中，ICC网络被破坏。神经胃肠病动态18，53-61,20064)我们也发现肠缺血再灌流模型小鼠的肠上皮细胞功能紊乱。J Surgical Research 135：255-261,20065)我们利用肿瘤坏死因子-a缺乏的小鼠确定了肿瘤坏死因子-a在肠道肌层炎症中的重要性。这一发现发表在《…》杂志上更多社论评论。在TNBS结肠炎模型中，在炎症停止后，被破坏的ICC网络被发现很快恢复。神经胃肠动力(1810191030,20067)和克罗恩病模型一样，发现CPI-17在溃疡性结肠炎模型中表达下调。神经胃肠病动态(19,504-514,20078)。应用组织化学技术，我们证实了在TNBS诱导的结肠炎模型中，ICC和神经网络均被破坏。组织化学细胞生物学127：41-53,20079)IL-1β诱导的CPI-17下调是通过利用肿瘤坏死因子α和IL-1α基因敲除小鼠二次产生肿瘤坏死因子α/β而实现的。Am J Physiol292：G1429-G1438,200710)我们发现IL-1β作为一种抗增殖介质，通过在真实的平滑肌组织中驻留的巨噬细胞产生前列腺素E_2和NO来间接起作用。Am J Physiol292：G1315-G1322,200711)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；动脉硬化性血栓形成血管生物学25；1796-1803,2005；动脉硬化血栓形成血管生物学25；1-7,2005；EUR J Pharmacol 515,134-141,2005等。较少

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