Studies on the regulatory mechanism of immuno-inflammatory responses by the euroendocrine system in the gastrointestinal mucosa, and the mucosal injury by the failure of this regulatory function.

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Our research group has studied the relationship between mucosal immune system and neuroendocrine system, and reported several important and leading research works. In the present research project, we aimed to clanify the regulatory mechanism in the intestinal mucosal defense and absorption functions from our idea for the close relationship between two systems, and the pathophysiological mechanism for the immuno-inflammatory disorders caused by the disturbance of this regulatory mechanism at the cellular or histological and molecular or genetical levels.In the gastrointestinal mucosa, macrophages in the lamina prepria play an important roled for uptaking and presenting intraluminal antigens. Urocortin, a mamarian member of the corticotropin-releasing factor (CRF) neuropeptide family and CRF receptor and their mRNA were detected in lamina propria macrophages from as early as three months of age at the time of the exposure to dietary intake and luminal bacteria after birth. CRF receptors … More werel also found in lamina propria mononuclear cells. Urocortin locally synthesized in lamina propria macrophages, together with CRF from hypothalamus, my act on lamina propria inflammatory cells as an autocrine/paracrine regulator of the mucosal immne system. In addition, the colonic mucosa from patients with irritable bowel syndrome, which is known to induced by psychological stress and also CRF infection, macrophages beneathe the mucosal surface epithelial layer were absent or much decreased and aggregated at the base of the mucosa. Eosinophils in the lamina propria increased (to be presented in DDW 2001 in US). Vasoatice intestinal peptide (VIP) and 11 β-hydroxysteroid dehydrogenases (11 βHSD) in the colonic mucosal play a cruicial roles in water and elecrolyte absorption. The present investigation found that VIP modulate directly the epithelial cell functions and 11 β HSD is also expressed by the colonic epithelia from 25 weeks gestion associated with differentiation or maturation in human colonic epithelia. Interestingly colonic epithelia in the ulcerative colitis patients lacked in these enzymes.These findings imply that immuno-inflammatory functions, in addition to aborption and movement of the gastrointestinal mucosa are ingeniously regulated by the neuro-endocrine system, and the failure of this regulation may cause various disorders of the gastrointestinal tract including immuno-inflammatory diseases. Less