ROLEs OF THE BRAIN-GUT-LIVER-IMMUNE AXIS IN NON-INFLAMMATORY ENVIRONMENIAL STRESS-INDUCED IMMUNEMODULATION.

脑-肠-肝-免疫轴在非炎症环境应激诱导的免疫调节中的作用。

基本信息

批准号：
10044302
负责人：
HORI Tetsuro
金额：
$ 2.24万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

In this project, in order to clarify the brain-gut-liver-immune-axis in terms of the neuroimmunomodulation under no-inflammatory stress, we, especially, focused on (1) the regulation of the membrane barrier in the gut, (2) the pathway from the gut associated organs to the central nervous system, (3) the brain mechanisms triggered by the peripheral inputs, mainly using in vivo rat model. Main results are summarized as follows.1) Mild non-inflammatory stresses such as immobilization, electrical foot shock, cage change stress, and heat exposure, induced plasma IL-6 increase.2) Non-inflammatory stress-induced plasma IL-6 increase appeared to be initiated by the gut-derived LPS.The evidence for this hypothesis were as follows.i) The LPS levels in the portal and systemic circulation were elevated during and after stresses.ii) The tissue LPS contents in the mesentery, mesenteric lymph nodes, liver, and spleen were increased during and after immobilization stress and electrical foot shock stre … More ss.iii) The non-inflammatory stress-induced plasma IL-6 elevation was attenuated by in vivo neutralization of bioactive LPS in circulation.iv) FITC-labeled LPS, which was injected into the lumen of the ileum through the cannulation implanted, was detected in the portal vein, and the total amount of the FITC-LPS translocated was increased by immobilization stress.v) About 80% of FITC-LPS positive cells in the liver was also observed IL-6 like immunoreactivity.vi) Tissue contents of the IL-6 mRNA in the liver was increased by immobilization stress, not in the spleen and the brain.vii) The IL-6 mRNA expression by in situ immunohistochemistry was dramatically increased in the liver3) Gelatin-binding-protein 28 (GBP28), which was released from the adipose tissue, could attenuated the LPS bioactivity in vitro, and expression of GBP28 was observed in the matrix of the connective tissue not only in the liver but other tissues. The data suggests that GBP28 functions as a scavenger for the gut derived LPS.4) The circulating LPS induced the IL-6 expression in the pituitary grand. Since the IL-6 receptor was detected in the LH and/or FSH cells, gut-derived LPS may modify the gonadotropic function.5) Gut derived LPS and/or bioactive substances induced by LPS reached to the circumventricular organs, which is connected with the hypothalamus in the brain. Less

在这个项目中，为了阐明非炎症应激下神经免疫调节的脑-肠-肝-免疫轴，我们特别关注（1）肠道膜屏障的调节，（2 ）从肠道相关器官到中枢神经系统的通路，（3）外周输入触发的脑机制，主要使用体内大鼠模型，主要结果总结如下。1）轻度非炎症应激，例如固定。 , 电击脚,笼子变化应激和热暴露诱导血浆 IL-6 增加。2) 非炎症应激诱导血浆 IL-6 增加似乎是由肠道来源的 LPS 引发的。这一假设的证据如下。 i)在压力期间和之后，门脉和体循环中的 LPS 水平升高。ii) 在固定压力和电足冲击压力期间和之后，肠系膜、肠系膜淋巴结、肝脏和脾脏中的组织 LPS 含量增加。 ss.iii) 非炎症应激诱导的血浆 IL-6 升高通过循环中生物活性 LPS 的体内中和而减弱。iv) 通过植入的插管将 FITC 标记的 LPS 注射到回肠腔中，在门静脉中检测到，固定应激使 FITC-LPS 易位总量增加。v) 肝脏中约 80% 的 FITC-LPS 阳性细胞也被检测到。观察到类似 IL-6 的免疫反应性。vi) 肝脏中 IL-6 mRNA 的组织含量因固定应激而增加，而脾脏和大脑中则没有。vii) 原位免疫组织化学显示 IL-6 mRNA 表达显着增加肝脏3）从脂肪组织中释放的明胶结合蛋白28（GBP28）可以在体外减弱LPS的生物活性，并且在肝脏中观察到GBP28的表达数据表明，GBP28 不仅在肝脏中，而且在其他组织中充当肠道来源的 LPS 的清除剂。4) 循环 LPS 诱导垂体中的 IL-6 表达。在 LH 和/或 FSH 细胞中检测到 6 受体，肠源性 LPS 可能会改变促性腺功能。 5) 肠源性 LPS 和/或 LPS 诱导的生物活性物质到达室周器官，与室周器官相关大脑中的下丘脑较少。