Dipartimento di Fisica Nucleare e Teorica, Università degli Studi di Pavia, 27100 Pavia, Italy.
Radiat Res. 2010 Sep;174(3):280-9. doi: 10.1667/RR1889.1.
Cell-to-cell signaling has become a significant issue in radiation biology due to experimental evidence, accumulated primarily since the early 1990s, of radiation-induced bystander effects. Several candidate mediators involved in cell-to-cell communication have been investigated and proposed as being responsible for this phenomenon, but the current investigation techniques (both theoretical and experimental) of the mechanisms involved, due to the particular set-up of each experiment, result in experimental data that often are not directly comparable. In this study, a comprehensive approach was adopted to describe cell-to-cell communication (focusing on cytokine signaling) and its modulation by external agents such as ionizing radiation. The aim was also to provide integrated theoretical instruments and experimental data to help in understanding the peculiarities of in vitro experiments. Theoretical/modeling activities were integrated with experimental measurements by (1) redesigning a cybernetic model (proposed in its original form in the 1950s) to frame cell-to-cell communication processes, (2) implementing and developing a mathematical model, and (3) designing and carrying out experiments to quantify key parameters involved in intercellular signaling (focusing as a pilot study on the release and decay of IL-6 molecules and their modulation by radiation). This formalization provides an interpretative framework for understanding the intercellular signaling and in particular for focusing on the study of cell-to-cell communication in a "step-by-step" approach. Under this model, the complex phenomenon of signal transmission was reduced where possible into independent processes to investigate them separately, providing an evaluation of the role of cell communication to guarantee and maintain the robustness of the in vitro experimental systems against the effects of perturbations.
由于实验证据的积累，尤其是自 20 世纪 90 年代初以来，辐射诱导的旁观者效应已成为放射生物学中的一个重要问题。已经研究了几种涉及细胞间通讯的候选介质，并提出它们是这种现象的原因，但由于每个实验的特定设置，目前涉及的机制的实验和理论研究技术导致实验数据通常无法直接比较。在这项研究中，采用了一种综合方法来描述细胞间通讯（侧重于细胞因子信号转导）及其受外部因素（如电离辐射）的调制。目的也是提供综合的理论工具和实验数据，以帮助理解体外实验的特点。理论/建模活动通过以下方式与实验测量相结合：（1）重新设计一个控制论模型（在 20 世纪 50 年代以其原始形式提出）来构建细胞间通讯过程，（2）实施和开发一个数学模型，以及（3）设计和进行实验以量化细胞间信号转导中涉及的关键参数（作为试点研究，重点关注 IL-6 分子的释放和衰减及其对辐射的调制）。这种形式化提供了一个解释性框架，用于理解细胞间信号转导，特别是用于聚焦于“逐步”方法研究细胞间通讯。在该模型下，信号传输的复杂现象尽可能地简化为独立的过程进行单独研究，从而评估细胞通讯的作用，以保证和维持体外实验系统的稳健性，防止受到干扰的影响。
