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

本研究旨在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疾病发病机制中的作用。1)尿皮质素是CRF家族的一种神经肽，在体内具有一定的CRF介导的生理作用，它定位于肠粘膜固有层的巨噬细胞中，这些巨噬细胞在炎症性疾病中增加。这表明PHA轴上的激素与细胞因子一起在胃肠道粘膜中起免疫调节作用。2)粘膜和粘膜下神经丛的大部分神经元含有VIP，其mRNA存在于上皮内内分泌细胞中。已知VIP调节巨噬细胞功能以及肠内水分分泌。炎性粘膜病变中VIP神经元分布不规则，数量减少。此外，在食物过敏合并过敏性皮炎的婴儿肠道黏膜中，肠粘膜中噬细胞和树突状细胞上的VIP受体外观恶化。3)矿盐皮质激素受体和11β -羟类固醇脱氢酶II型在包括结肠上皮细胞在内的参与离子和/或水转运的相同细胞中表达。它们在溃疡性结肠炎结肠粘膜再生细胞中的表达消失。提示溃疡性结肠炎中离子和水的表达紊乱是由它们的表达缺失引起的。4)幽门螺杆菌感染的胃粘膜小凹上皮细胞出现一些DNA异常，包括巨噬细胞和中性细胞浸润引起的凋亡。vip神经元变得不规则并减少。

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.