| Research Abstract |
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, 2005
2) 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, 2006
3) We found that ICC networks were destroyed in the artificial intestinal obstruction model in rat. Neurogastroenterology Motility 18, 53-61, 2006
4) We also found the ICC disorder in intestinal ischemia-reperfusion model mice. J Surgical Research 135 : 255-261, 2006
5) 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
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Editorial Comment. Neurogastroenterology Motility 18, 578-588, 2006
6) 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, 2006
7) As well as Crohn's disease model, CPI-17 was found to be down regulated in ulcerative colitis model. Neurogastroenterology Motility 19, 504-514, 2007
8) 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, 2007
9) 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, 2007
10) 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, 2007
11) 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
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