Babini G, Morini J, Baiocco G, Mariotti L, Ottolenghi A
1] Department of Physics, University of Pavia, Pavia, Italy [2] INFN, National Institute of Nuclear Physics, Sezione di Pavia, Pavia, Italy.
1] Department of Physics, University of Pavia, Pavia, Italy [2] INFN, National Institute of Nuclear Physics, Sezione di Pavia, Pavia, Italy [3] Department of Molecular Medicine, Biology and Medical Genetics Unit, University of Pavia, Pavia, Italy.
Sci Rep. 2015 Mar 20;5:9343. doi: 10.1038/srep09343.
The inflammatory pathway has a pivotal role in regulating the fate and functions of cells after a wide range of stimuli, including ionizing radiation. However, the molecular mechanisms governing such responses have not been completely elucidated yet. In particular, the complex activation dynamics of the Nuclear transcription Factor kB (NF-kB), the key molecule governing the inflammatory pathway, still lacks a complete characterization. In this work we focused on the activation dynamics of the NF-kB (subunit p65) pathway following different stimuli. Quantitative measurements of NF-kB were performed and results interpreted within a systems theory approach, based on the negative feedback loop feature of this pathway. Time-series data of nuclear NF-kB concentration showed no evidence of γ-ray induced activation of the pathway for doses up to 5 Gy but highlighted important transient effects of common environmental stress (e.g. CO2, temperature) and laboratory procedures, e.g. replacing the culture medium, which dominate the in vitro inflammatory response.
炎症信号通路在包括电离辐射在内的多种刺激后调节细胞的命运和功能方面起着关键作用。然而,控制这种反应的分子机制尚未完全阐明。特别是,作为炎症信号通路关键分子的核转录因子κB(NF-κB)的复杂激活动力学仍缺乏完整的表征。在这项工作中,我们专注于不同刺激后NF-κB(亚基p65)信号通路的激活动力学。我们对NF-κB进行了定量测量,并基于该信号通路的负反馈回路特征,采用系统理论方法对结果进行了解释。细胞核NF-κB浓度的时间序列数据表明,在高达5 Gy的剂量下,没有证据显示γ射线会诱导该信号通路的激活,但突出了常见环境应激(如二氧化碳、温度)和实验室操作(如更换培养基)的重要瞬时效应,这些因素主导了体外炎症反应。