Hu Dan, Zhang Yan, Cao Ruiqi, Hao Yuying, Yang Xiaoye, Tian Tiantian, Zhang Jiandong
Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
Department of Physiology, Jeonbuk National University Medical School, Jeonju, Korea.
Transl Lung Cancer Res. 2020 Dec;9(6):2440-2459. doi: 10.21037/tlcr-20-1272.
Radiation-induced lung injury (RILI) is a common complication of thoracic cancer radiation therapy. Currently, there is no effective treatment for RILI. RILI is associated with chronic inflammation, this injury is perpetuated by the stimulation of chemokines and proinflammatory cytokines. Recent studies have demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a pivotal role in inflammation and fibrosis. This study aimed to investigate the protective effect of GM-CSF against the development of RILI in lung tissue.
First, a single fraction of radiation at a dose of 16 Gy was targeted at the entire thorax of wild-type (WT) C57BL/6 mice and GM-CSF mice to induce RILI. Second, we detected the radioprotective effects of GM-CSF by measuring the inflammatory biomarkers and fibrosis alteration on radiated lung tissues. Furthermore, we investigated the potential mechanism of GM-CSF protective effects in RILI.
The GM-CSF mice sustained more severe RILI than the WT mice. RILI was significantly alleviated by GM-CSF treatment. Intraperitoneally administered GM-CSF significantly inhibited inflammatory cytokine production and decreased epithelial-mesenchymal transition (EMT) in the RILI mouse model.
GM-CSF was shown to be an important modulator of RILI through regulating inflammatory cytokines, which provides a new strategy for the prevention and treatment of RILI.
放射性肺损伤(RILI)是胸段癌放射治疗的常见并发症。目前,尚无针对RILI的有效治疗方法。RILI与慢性炎症相关,这种损伤通过趋化因子和促炎细胞因子的刺激而持续存在。最近的研究表明,粒细胞巨噬细胞集落刺激因子(GM-CSF)在炎症和纤维化中起关键作用。本研究旨在探讨GM-CSF对肺组织中RILI发生发展的保护作用。
首先,以16 Gy的单次辐射剂量照射野生型(WT)C57BL/6小鼠和GM-CSF小鼠的整个胸部以诱导RILI。其次,我们通过测量辐射肺组织中的炎症生物标志物和纤维化改变来检测GM-CSF的辐射防护作用。此外,我们研究了GM-CSF在RILI中发挥保护作用的潜在机制。
GM-CSF小鼠比WT小鼠遭受更严重的RILI。GM-CSF治疗可显著减轻RILI。在RILI小鼠模型中,腹腔注射GM-CSF可显著抑制炎性细胞因子的产生并减少上皮-间质转化(EMT)。
GM-CSF通过调节炎性细胞因子被证明是RILI的重要调节因子,这为RILI的预防和治疗提供了新策略。