CENTARAL AND PERIPHERAL MECHANISMS IN THE HOST DEFENSE FUNCTION AGAINST NON-INFLAMMATORY ENVIRONMENTAL STRESS.

宿主防御非炎症环境应激的中枢和外周机制。

基本信息

批准号：
10307001
负责人：
HORI Tetsuro
金额：
$ 20.22万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
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, we intended to claryfy the central and peripheral mechanisms in terms of host defense functions under non-inflammatory environmental stress. Main results are summarized as follows.1) Proposal of a new host-defense paradigm/the brain-gut-liver-immune axisThe non-inflammatory stress induced the change of gut membrane barrier sysytem, then gut-derived endotoxin come into the inside of the barrier sysytem (stress-induced LPS translocation). Stress-induced LPS translocation in the gut acitivate the immune network resulting in up regulation of the host=defense function againt the stress.2) The effect of brain-derived IL-1 on the noradrenargic (NA) sysytemThe release of NA in the frontal brain during the immobilization stress is mediated by the IL-I, PGE2, NO, and Glutamate.3) Modification of brain-derived cytokines on the mechanisms of noticeptionAdministration of cytokines into the brain changed the threshold the notiception.4) Expression of cytokines and c-fos in the brain during the non-inflammatory stressesThe c-fos mRNA expression in the POA, LHA, VMH in the brain was increased by cold exposure. The CRF mRNA expression in the MPO and PVN was increased by heat exposure, and that in the POA and LHA was increased by cold exposure. The microinjection of the antisense-oligo DNA for the c-fos into the POA inhibited the expression of IFN mRNA in the brain.5) The shift of subsets of periferal lymphocytes during the non-inflammatory stressesThe head down stress during one hour induced the CD4+ Tcell increase, CD4/8 increase. However, six hour later, CD8+ T cell decrease and B cell increase was observed.

在这个项目中，我们旨在阐明非炎症环境应激下宿主防御功能的中枢和外周机制。主要结果如下： 1）提出一种新的宿主防御范式/脑-肠-肝-免疫轴非炎症应激诱导肠膜屏障系统的变化，肠源性内毒素进入机体内部。屏障系统（应激诱导的 LPS 易位）。肠道内压力诱导的 LPS 易位激活免疫网络，导致宿主的上调=针对压力的防御功能。2) 脑源性 IL-1 对去甲肾上腺素 (NA) 系统的影响额叶中 NA 的释放固定应激期间的大脑由IL-I、PGE2、NO和谷氨酸介导。3)脑源性细胞因子对感知机制的修饰4)非炎症应激时脑内细胞因子和c-fos的表达冷暴露后脑内POA、LHA、VMH中c-fos mRNA表达增加。热暴露使 MPO 和 PVN 中 CRF mRNA 表达增加，冷暴露使 POA 和 LHA 中 CRF mRNA 表达增加。将c-fos的反义寡聚DNA显微注射到POA中抑制了脑中IFN mRNA的表达。5)非炎症应激过程中周围淋巴细胞亚群的变化1小时内低头应激诱导CD4+ T细胞增加，CD4/8增加。然而，六小时后，观察到 CD8+ T 细胞减少，B 细胞增加。