Department of Radiotherapy and Radiation Oncology, University Medical Center Rostock, Südring 75, 18059 Rostock, Germany.
J Immunol Res. 2018 Jun 3;2018:2856518. doi: 10.1155/2018/2856518. eCollection 2018.
In many European countries, patients with a variety of chronical inflammatory diseases are treated with low-dose radiotherapy (LD-RT). In contrast to high-dose irradiation given to tumor patients, little is known about radiobiological mechanisms underlying this clinical successful LD-RT application. The objective of this study was to gain a better insight into the modulation of inflammatory reactions after LD-RT on the basis of endothelial cells (EC) as major participants and regulators of inflammation.
Three murine EC lines were cultivated under 2D and 3D culture conditions and irradiated with doses from 0.01 Gy to 2 Gy. To simulate an inflammatory situation, cells were activated with TNF-. After LD-RT, a screening of numerous inflammatory markers was determined by multiplex assay, followed by detailed analyses of four cytokines (KC, MCP-1, RANTES, and G-CSF). Additionally, the monocyte binding to EC was analyzed.
Cytokine concentrations were dependent on culture condition, IR dose, time point after IR, and EC origin. IR caused nonlinear dose-dependent effects on secretion of the proinflammatory cytokines KC, MCP-1, and RANTES. The monocyte adhesion was significantly enhanced after IR as well as activation.
The study shows that LD-RT, also using very low radiation doses, has a clear immunomodulatory effect on EC as major participants and regulators of inflammation.
在许多欧洲国家,患有各种慢性炎症性疾病的患者接受低剂量放射治疗(LD-RT)。与给予肿瘤患者的高剂量照射相比,人们对这种临床成功的 LD-RT 应用背后的放射生物学机制知之甚少。本研究的目的是基于内皮细胞(EC)作为炎症的主要参与者和调节者,更好地了解 LD-RT 后炎症反应的调节。
将三种鼠源 EC 系在 2D 和 3D 培养条件下培养,并以 0.01Gy 至 2Gy 的剂量照射。为了模拟炎症情况,用 TNF-激活细胞。LD-RT 后,通过多重分析测定多种炎症标志物的筛选,然后对四种细胞因子(KC、MCP-1、RANTES 和 G-CSF)进行详细分析。此外,还分析了单核细胞与 EC 的结合。
细胞因子浓度取决于培养条件、IR 剂量、IR 后时间点和 EC 来源。IR 对促炎细胞因子 KC、MCP-1 和 RANTES 的分泌产生非线性剂量依赖性影响。IR 后以及激活后单核细胞的黏附明显增强。
该研究表明,LD-RT 甚至使用非常低的辐射剂量,对作为炎症主要参与者和调节剂的 EC 具有明显的免疫调节作用。