TLR-TRIF mediated induction of GLI3 modulates innate inflammatory responses

TLR-TRIF 介导的 GLI3 诱导调节先天炎症反应

• 批准号: 10179420
• 负责人: Sherine F. Elsawa
• 金额: $ 30.2万
• 依托单位: UNIVERSITY OF NEW HAMPSHIRE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2023-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10179420
• 关键词: Biomedical Engineering; Chronic; Disease; GLI3 gene; Inflammation; Inflammatory; Inflammatory Response; Innate Immune Response; Mediating; Molecular; Pathway interactions; Phenotype; Production; Regulation; Research; Role; Signal Transduction; 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症的表达和分泌 有助于消灭感染病原体的细胞因子。细胞因子失调 产生（慢性炎症）会对宿主产生负面影响。因此，一个基本的 了解调节炎症的分子机制对于炎症的发展至关重要 炎症性疾病的治疗方法。我们确定了转录因子的新作用 GLI3 响应 TLR-TRIF 信号传导调节细胞因子表达。单核细胞中的 GLI3 KO 诱导 表明 GLI3 与响应 TLR-TRIF 的炎症途径相关的表型 刺激。在本提案中，我们将进一步阐明GLI3在调节细胞因子表达中的作用 单核细胞并探索这种调节在炎症反应中的相关性。