MECHANISMS OF PRETERM LABOR: NF-KB ACTIVATION OF COX-2

早产的机制：NF-KB 激活 COX-2

• 批准号: 2883168
• 负责人: DOUGLAS A KNISS
• 金额: $ 23.67万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2883168
• 关键词: DNA binding protein; SDS polyacrylamide gel electrophoresis; antisense nucleic acid; autoradiography; densitometry; enzyme activity; gel mobility shift assay; gene expression; gestational age; hormone regulation /control mechanism; human tissue; immunocytochemistry; immunoprecipitation; interleukin 1; laboratory mouse; northern blottings; nuclear factor kappa beta; phosphorylation; polymerase chain reaction; premature labor; prostaglandin endoperoxide synthase; regulatory gene; statistics /biometry; tissue /cell culture; tumor necrosis factor alpha; western blottings

DESCRIPTION (Adapted from the applicant's abstract): In this proposal, the investigator will test the hypothesis that cytokines IL-1b and TNF-a govern COX-2 gene expression via the transcription factor nuclear factor-kB (NF-kB). Using amnion-derived WISH cells as a model system, they will examine whether NF-kB is activated following cytokine challenge. In addition, they will determine whether cytokine treatment leads to phosphorylation and degradation of 1kBa, the inhibitor protein bound to inactive NF-kB, as part of the activation process. Antisense strategies will be employed to determine the effect of ablating NF-kB subunits on COX-2 inducibility by cytokines. The proposal will also use a murine model of PTL induced by endotoxin to explore whether NF-kB activation of the COX-2 gene functions in vivo. Finally, the investigator will test the hypothesis by examining whether nuclear extracts from intrauterine tissues obtained from women in PTL contain activated NF-kB compared with tissues from women of the same gestational age but not in labor.

描述（根据申请人的摘要改编）：在此提案中 研究者将测试细胞因子IL-1B和TNF-A控制的假设 COX-2基因通过转录因子核因子-KB表达 （NF-KB）。 将羊膜来源的愿望单元作为模型系统，它们将 检查在细胞因子挑战之后是否激活NF-KB。 在 此外，他们还将确定细胞因子治疗是否导致 1KBA的磷酸化和降解，抑制剂蛋白与 作为激活过程的一部分，非活性NF-KB。 反义策略 将被用来确定烧蚀NF-KB亚基对COX-2的影响 细胞因子诱导性。 该提案还将使用PTL的鼠模型 通过内毒素诱导的探索COX-2基因的NF-KB是否激活 体内功能。 最后，研究人员将通过 检查是否从宫内组织中获得的核提取物。 与女性的组织相比，PTL中的女性包含活化的NF-KB 同一胎龄，但没有劳动。