Enteric endotoxine as a intrinsic humoral factor and environmental stress

肠内毒素作为内在体液因子和环境应激

• 批准号: 12670061
• 负责人: TAKAKI Atsushi
• 金额: $ 2.18万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670061/
• 关键词: endotoxin; lipopolysccharide; LPS translocation; Pituitary; Apoptosis; IL-6; DNA oxidative damage; 8OHdG

It has long been known that plasma intereukin (IL)-6 levels elevate during non inflammatory, physico/ psychological stresses such as immobiliztion (1MB) and electric foot shock. (FS) We previously demonstrated that an IMB-induced rise in plasma IL-6 in the rat was caused, at least partly, by an increased production of IL-6 in hepatic reticuloendothelial cells which were induced by enteric flora derived lipopolysccharide (LPS). This study investigated whether such enteric flora-derived LPS may produce IL-6 also in the mesentery and the mesenteric lymphoid nodes (MLN) before it reaches the liver. We found a rise in the IL-6 levels in the hepato- portal vein (PV) within 30 min during FS, while the IL-6 levels in thejugular vein showed a smaller and delayed rise with slower recovery. Plasma IL-6 levels near the exit of the hepatic vein in the inferior vena cava was highest at both control and stressed conditions, compared with those in the PV and any other extra-hepatic circulation. The stress-induced IL-6 elevation in the PV was abolished by an in vivo neutralization of LPS with continuous infusion of polymyxin B. Furthermore, the amount of LPS as assessed by its bioactivity increased rapidly in the mesentery, the MLN and the liver within 15 min after the start of FS. Finally, fluorescent dye-labeled LPS infused into the lumen of the ileum was found in the extraintestinal tissues and systemic vein, and FS increased the optical density. The findings suggest that these lymphoid organs are continuously exposed to LPS at the basal condition and FS facilitates the LPS/bacterial translocation across the intestinal wall and thereby increases the production of IL-6 in the gut associated lymphoid organs before LPS reaches the liver.In addition to this, we claryfied the roles of LPS on pituitary cells, DNA oxidative damages, etc, in this project. We can summarize the LPS act as a key mediator to establish and keep the host-defense mechanism like an intrinsic humoral factor.

人们早就知道血浆白细胞介素 (IL)-6 水平在非炎症、生理/心理压力（如固定 (1MB) 和电足电击）期间升高。 (FS) 我们之前证明，IMB 诱导的大鼠血浆 IL-6 升高至少部分是由肠内菌群衍生的脂多糖 (LPS) 诱导的肝网状内皮细胞中 IL-6 的产生增加引起的。这项研究调查了这种肠道菌群来源的 LPS 是否也可能在到达肝脏之前在肠系膜和肠系膜淋巴结 (MLN) 中产生 IL-6。我们发现肝门静脉 (PV) 中的 IL-6 水平在 FS 期间 30 分钟内上升，而颈静脉中的 IL-6 水平显示出较小且延迟的上升，且恢复较慢。与 PV 和任何其他肝外循环中的血浆 IL-6 水平相比，下腔静脉中肝静脉出口附近的血浆 IL-6 水平在对照和应激条件下均最高。通过持续输注多粘菌素 B 体内中和 LPS，可以消除应激诱导的 PV 中 IL-6 升高。此外，根据其生物活性评估，在 FS 开始后 15 分钟内，肠系膜、MLN 和肝脏中的 LPS 量迅速增加。最后，在肠外组织和全身静脉中发现注入回肠管腔的荧光染料标记的LPS，并且FS增加了光密度。研究结果表明，这些淋巴器官在基础条件下持续暴露于LPS，FS促进LPS/细菌跨肠壁易位，从而在LPS到达肝脏之前增加肠道相关淋巴器官中IL-6的产生。除此之外，我们在本项目中阐明了LPS对垂体细胞、DNA氧化损伤等的作用。我们可以将LPS总结为像内在体液因子一样作为建立和维持宿主防御机制的关键介质。

项目成果

Yagi S et al.: "Enteric lipopolysaccharide raises plasma IL-6 levels in the hepatopotal vein during non-inflammatory stress in rat"福岡医学会雑誌. (In press). (2002)

Yagi S 等人：“肠脂多糖在大鼠非炎症应激期间提高肝静脉中的血浆 IL-6 水平”《福冈医学会杂志》（2002 年出版）。

N.Sudo, A.Takaki, C.Kubo et al.: "Dietary nucleic acid promote a shift in Th1/Th2 balance tward Th-1 dominant immunity"Clinical Exp. Allergy. 30. 979-987 (2000)

N.Sudo、A.Takaki、C.Kubo 等人：“饮食核酸促进 Th1/Th2 平衡向 Th-1 显性免疫的转变”临床实验。

T. Katafuchi, A. Takaki, T. Kondo, and T. Hori: "Changes in brain cytokine mRNA due to heat stress in aged rats : possible role of bacterial translocation"Physical Fitness and Health Promotion in Active Aging, edited by K. Shiraki, S. Sagawa, and M.K. You

T. Katafuchi、A. Takaki、T. Kondo 和 T. Hori：“老年大鼠热应激引起的脑细胞因子 mRNA 的变化：细菌易位的可能作用”《积极老龄化中的身体健康与健康促进》，K.

Y.Yagi, A.Takaki, et al.: "Entenc lipopolysaccharide raises plasma IL-6 levels in the hepatoportal vein during non-inflammatory stress in the rat"Fukuoka Acta Med. 93(3). 38-52 (2002)

Y.Yagi、A.Takaki 等人：“Entenc 脂多糖在大鼠非炎症应激期间提高肝门静脉血浆 IL-6 水平”Fukuoka Acta Med。

N. Sudo, Y. Aiba, A. Takaki, K. Tanaka, X.-N. Yu, N. Oyama, Y. Koga, and C. Kubo: "Dietary nucleic acid promote a shift in Th1/Th2 balance tward Th-1 dominant immunity"Clinical Exp. Allergy. Vol.30. 979-987 (2000)

N.须藤，Y.相叶，A.高木，K.田中，X.-N。