Molecular mechanisms underlying a distinct specific response mediated by IFNbeta and TNFalpha costimulation.

IFNβ 和 TNFα 共刺激介导的独特特异性反应的分子机制。

• 批准号: 355306-2012
• 负责人: Grandvaux, Nathalie
• 金额: $ 2.91万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=527730
• 关键词: Molecular; mechanisms; underlying; distinct; specific

Cytokines are soluble mediators produced by cells to transmit signal of danger to activate an appropriate biological response. This response is ultimately linked to the activation of transcription factors that are responsible for the expression of a panel of specific genes. The molecular mechanisms that explain how a specific cytokine triggers a specific molecular pathway have been the focus of numerous studies over the past decades. However, in a physiological situation it is highly unlikely that a cell is stimulated by one cytokine at a time. Instead, a cell simultaneously responds to a "cocktail of cytokines" that are produced simultaneously by the same stimulus. What happens in this condition of costimulation is of particular importance to understand the functions of cytokines, but still remains to be elucidated. Using as a prototype the costimulation by two cytokines named Interferon ß and Tumor Necrosis Factor a both produced in response to various stimuli, our research led us to uncover a novel specific molecular pathway mediating the expression of distinct genes. We propose to fully characterize this novel mechanism that will shed a new light in our understanding of how cells respond to cytokines in a physiological situation.

细胞因子是由细胞产生的可溶性介质，用于传递危险信号以激活适当的生物反应。这种反应最终与负责一组特定基因表达的转录因子的激活有关。解释特定细胞因子如何触发特定分子途径的分子机制在过去几十年中一直是众多研究的焦点。然而，在生理情况下，细胞一次被一种细胞因子刺激是极不可能的。相反，细胞同时响应于由相同刺激同时产生的“细胞因子鸡尾酒”。在这种共刺激条件下发生的情况对于理解细胞因子的功能特别重要，但仍有待阐明。以干扰素α和肿瘤坏死因子α这两种细胞因子对各种刺激的共刺激为原型，我们的研究揭示了一种新的介导不同基因表达的特异性分子途径。我们建议充分表征这种新的机制，这将为我们理解细胞在生理情况下如何响应细胞因子提供新的思路。