The critical role of bromodomain proteins TgBDP1 and TgBDP2 in regulating gene expression in the protozoan parasite Toxoplasma gondii

溴结构域蛋白 TgBDP1 和 TgBDP2 在调节原生动物寄生虫弓形虫基因表达中的关键作用

• 批准号: 10176697
• 负责人: Victoria Jeffers
• 金额: $ 23.86万
• 依托单位: UNIVERSITY OF NEW HAMPSHIRE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10176697
• 关键词: Biomedical Engineering; Bromodomain; Chronic; Disease; GLI3 gene; Gene Expression; Inflammation; Inflammatory; Inflammatory Response; Innate Immune Response; Molecular; Parasites; Pathway interactions; Phenotype; Production; Proteins; Regulation; Research; Role; Signal Transduction; Toxoplasma gondii; cytokine; monocyte; novel; pathogen; response; therapeutic development; transcription factor

The innate immune response to pathogens involves the expression and secretion of inflammatory cytokines that act to facilitate eradication of the infecting pathogen. The dysregulation of cytokine production (chronic inflammation) can have negative effects on the host. Therefore, a fundamental understanding of the molecular mechanisms regulating inflammation is essential for the development of therapeutic approaches for inflammatory disorders. We identify a novel role for the transcription factor GLI3 in regulating cytokine expression in response to TLR-TRIF signaling. GLI3 KO in monocytes induces a phenotype that indicates GLI3 associates with inflammatory pathways in response to TLR-TRIF stimulation. In this proposal, we will further elucidate the role of GLI3 in regulating cytokine expression in monocytes and explore the relevance of this regulation in inflammatory responses.

对病原体的先天免疫反应涉及炎性物质的表达和分泌 有助于根除感染病原体的细胞因子。细胞因子的失调 产生(慢性炎症)会对宿主产生负面影响。因此，一个根本的 了解调节炎症的分子机制对于发展 炎症性疾病的治疗方法。我们确定了转录因子的一个新角色 GLI3在调节TLR-TRIF信号通路中的细胞因子表达。单核细胞内GLi3 KO诱导 一种表明GLI3与TLR-TRIF反应的炎症途径相关的表型 刺激。在这项建议中，我们将进一步阐明GLI3在调节细胞因子表达中的作用。 并探讨这一调节在炎症反应中的相关性。