INDUCTION OF HEAT SHOCK PROTEIN BY INTERLEUKIN 1 INTRAAMNIOTIC INFUSION

羊膜腔内输注白细胞介素 1 诱导热休克蛋白

• 批准号: 6277397
• 负责人: MICHAEL G GRAVETT
• 金额: $ 7.42万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277397
• 关键词: Mammalia; Primates; bacteria; clinical research; endocrine gland /system; immunology; infant mortality; infection; inflammation; low birth weight infant human; mother /infant health care; reproductive system; women's health

Induction of proinflammatory cytokine synthesis leading to prostaglandin production and myometrial contractions is an established pathway of infection-related preterm labor. The mechanisms limiting cytokine-induced preterm contractions have only recently been investigated. Interleukin-1 (IL-1) receptor antagonist has been identified in amniotic fluid (AF) and shown to increase in concentration following cytokine activation. We now report that infusion of IL-1 into the AF also induces synthesis of heat shock protein (HSP). Induction of HSP gene transcription has been shown to inhibit transcription of the IL-1 and tumor necrosis factor (TNF) genes. Chronically instrumented rhesus macaques with timed gestations were infused with recombinant human IL-1b. At timed intervals AF was obtained and IL-1, TNF, and IL-6 concentrations were determined. Levels of the 60kD HSP were determined by EIA using monoclonal antibodies to human HSP. Amniotic fluid was also tested for the presence of 60kD and 70kD HSP by Western blots. Prior to infusion, TNF, IL-6, and HSP were undetectable in AF. Following IL-1 infusion, AF TNF and IL-6 levels quickly rose. A 60kD HSP appeared in AF coincident with decreasing intraamniotic concentrations of TNF and IL-6. In 4 monkeys, peak AF HSP concentrations of 1-5 ng/ml were estimated using a standard curve generated with human HSP. Western blot analysis confirmed the absence of HSP in AF prior to IL-1 infusion and the appearance of 60kD and 70kD HSP in AF following infusion. Thus, induction of HSP synthesis in the amniotic cavity by proinflammatory cytokines may be another regulatory mechanism to limit cytokine synthesis and the subsequent cascade leading to preterm contractions.

促炎细胞因子合成的诱导导致 前列腺素的产生和子宫肌层的收缩是一个既定的 感染相关早产的途径。 限制机制 尼古丁引起的早产收缩最近才被 研究了 白细胞介素-1（IL-1）受体拮抗剂已被 在羊水（AF）中发现， 细胞因子活化后的浓度。 我们现在报告， 将IL-1输注到AF中也诱导热休克的合成 蛋白（HSP）。 HSP基因转录的诱导已被证明是 抑制IL-1和肿瘤坏死因子（TNF）的转录 基因. 具有定时妊娠的慢性仪器化恒河猴 输注重组人IL-1b。 在定时间隔AF是 并测定IL-1、TNF和IL-6浓度。 用单克隆抗体酶免疫分析法测定60 kD HSP的水平， 人HSP抗体。 还对羊水进行了检测， Western blot检测60 kD和70 kD HSP的表达。 输注前， TNF、IL-6和HSP在AF中检测不到。 AF TNF和IL-6水平迅速升高。 AF中出现60 kD HSP 与羊膜内TNF浓度降低一致， IL-6。 在4只猴子中，1-5 ng/ml的峰值AF HSP浓度为 使用人HSP产生的标准曲线估计。 西方 印迹分析证实，在IL-1之前，AF中不存在HSP 房颤时60 kD和70 kD HSP的出现 输液 因此，在羊膜腔内HSP合成的诱导， 促炎细胞因子可能是另一种调节机制， 细胞因子的合成和随后的级联反应导致早产 宫缩