Regulation of GI motility by cross-talk with nerve, pace maker anti immune cells

肠道运动受几个系统的控制，包括神经源性、肌源性和内分泌系统。近年来的形态和功能研究表明，Cajal间质细胞(ICCs)是胃肠道肌肉系统的起搏器。ICCs以独特的模式排列，与肌层中的神经和平滑肌细胞关系密切，并产生起搏电流，在胃肠道平滑肌中形成电慢波。此外，肌层内的巨噬细胞有规律地分布在浆膜下和肌间神经丛水平。然而，这些细胞如何协同作用于胃肠道运动仍有待确定。在本研究中，我们获得了以下结果：1)克罗恩病模型(TNBS治疗)大鼠结肠环状平滑肌自发收缩和蠕动的抑制是由于ICCs和肌间神经系统的损害。巨噬细胞活化的迹象及其与巨噬细胞聚集的密切关系表明，巨噬细胞在肠道运动退行性病变中起重要作用。2)结肠炎大鼠结肠环状平滑肌收缩减弱与L钙通道活性降低有关。L型钙通道的功能障碍可能是通过依赖于NF-κB的途径来实现的。3)以巨噬细胞为主要来源的IL-1可抑制CPI17的表达或MYPTI的磷酸化，从而增加肌球蛋白磷酸酶的活性，从而减少力量的产生。IL-1-可能是IBD等胃肠动力紊乱的重要介质。

Intestinal motility is under the control of several systems, including the neurogenic, myogenic and endocrine systems. Morphological and functional studies in recent years have suggested that interstitial cells of Cajal (ICCs) are pacemakers in the musculature of the gastrointestinal tract. ICCs are arranged in distinctive patterns in close relation to nerve and smooth muscle cells in the muscle layer, and generate pacemaker currents to develop electrical slow waves in the gastrointestinal smooth muscles. In addition, muscularis resident macrophages are regularly distributed in the subserosa and at the level of the myenteric plexus. However, it remains to be determined how these cells coordinately contribute to the GI motility. In this study, we have obtained the following results :1)Inhibition of spontaneous contractions and peristalsis in circular smooth muscle from the colons of Crohn's disease model (TNBS-treated) rats is attributable to the impairment of ICCs and myenteric nerve systems. The indication of macrophage activation and the close correlation between the degeneration and macrophage accumulation suggest that the macrophages play critical a role in the degenerative pathology of intestinal motility.2)Decrease in the contraction of circular smooth muscle isolated from TNBS induced colitis rat colon is attributable to the decreased activity of the L type Ca-channel. The dysfunction of the L type Ca-channel may be mediated by NF-κB-dependent pathways.3)Treatment, of smooth muscle with IL-1□, which is derived mainly from macrophages, decreases either CPI-17 expression or MYPT I phosphorylation, which results in an increase in myosin phosphatase activity to reduce force generation. IL-1□ could be an important mediator of gastrointestinal motility disorders in IBD, etc.