Closs talk between neuroendocrine and mucosal immune systems in the gastrointestinal mucosa and its disorder

本研究的目的是阐明神经内分泌系统与粘膜免疫系统相互作用的机制，并了解神经内分泌-免疫相互作用异常在胃肠道粘膜炎症和肿瘤性疾病发病机制中的作用。1）尿皮质素（Urocortin），CRF家族的一种神经肽，在体内表现出CRF介导的生理作用，巨噬细胞主要分布于胃粘膜固有层，炎性病变时巨噬细胞增多。提示PHA轴中的VIP与细胞因子一起在胃肠道粘膜中发挥免疫调节作用。2）粘膜和粘膜下神经丛的大部分神经元含有VIP，其mRNA存在于上皮内分泌细胞中。已知VIP调节巨噬细胞功能以及肠中的水分泌。在炎性粘膜病变中，VIP神经元的分布变得不规则，数量减少。此外，食物过敏合并特发性皮炎患儿肠黏膜中的噬菌体和树突状细胞上VIP受体的出现，在肠黏膜中也发生了退化。3）盐皮质激素受体和11 β-羟类固醇脱氢酶II型在参与离子和/或水转运的相同细胞中表达，包括结肠上皮细胞。在溃疡性结肠炎的结肠粘膜再生细胞中，它们的表达消失。提示溃疡性结肠炎时细胞内水、离子平衡紊乱是由于它们的表达缺失所致。4）幽门螺杆菌感染胃粘膜的小凹上皮细胞出现了一些DNA异常，包括巨噬细胞诱导的细胞凋亡和中性粒细胞浸润。VIP神经元变得不规则，减少。

The aim of this study is to clarify the mechanism for interations between the neuroendocrine system and the mucosal immune system, and also to understand roles of abnormalities of the neuroendocrine-immune interactions in the pathogenesis of inflammatory and neoplastic disorders in the gastrointestinal mucosa.1) Urocortin, a neuropeptide of CRF family showing some physiological CRF-mediated actions in vivo, was localized in macrophages is the lamina propria of the intestnial mucosa, and these macrophages were increased in the inflammatory disotders. This suggests that hormons in the PHA axis play a immunoregulatory roles in the gastrointestinal mucosa, together with cytokines.2) The majority of neurons of the mucosal and submucosal plexus contained VIP,and its mRNA was found in intraepithelial endocrine cells. VIP is known to regulate macrophage funcions as well as water secretion in the intestine. In inflammatory mucosal lesions, distribution of VIP neurons became irregular and decreased in the number. In addition, appearance of VIP receptor on marophages and dendritic cells in the intestiral mucosa deteriorated in the intestinal mucosa from the infants with food allergy combined with atpic dermatitis.3) Mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type II were expressed in the same cells participating ion and /or water transport including colonic epithelial cells. Their expression disappeared in regenerating cells in the colonic mucosa with ulcerative colitis. This suggests that the disturbance of ion and water vlance in the ulcerative colitis is caused by the absence of their expression.4) Foveolar epithelial cells of H.pylori-infected gastric mucosa showed some DNA abnormalities incleding apoptosis induced by macrophage and neutropic infiltration. VIP-neurons became irregular and were decreased.