STING facilitates the development of radiation-induced lung injury via regulating the PERK/eIF2α pathway

作者：Xiangwei Ge, Qiaowei Liu, Hao Fan, Hongyang Yu, Jinfeng Li, Yao Li, Boyu Qin, Junxun Ma, Jinliang Wang, Yi Hu · 发表于：Translational Lung Cancer Research · 年份：2024 · DOI：10.21037/tlcr-24-649 · 被引用次数：9 · 研究领域：interferon and immune responses、Endoplasmic Reticulum Stress and Disease、Effects of Radiation Exposure

Background: Radiation-induced lung injury (RILI) is one of the serious adverse reactions of thoracic radiotherapy, which largely limits the dose and therapeutic effect of radiotherapy. The underlying mechanism has not been elucidated. RILI is characterized by an acute inflammatory response, and stimulator of interferon genes (STING) has been reported to play an important role in regulating inflammation and innate immune activation. However, its role in RLLI, remains unclear. Here, we reported the potential therapeutic effect of STING inhibitor H-151 on RILI. Methods: C57BL/6J mice were exposed to 20 Gy whole-thorax irradiation and H-151 was injected intraperitoneally from the day of irradiation for 4 weeks. The degree of RILI was then assessed. To further explore the mechanism of STING in RILI, the supernatant of irradiated lung epithelial cell MLE-12 was co-cultured with embryonic fibroblast cell NIH/3T3. Results: The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-STING pathway is abnormally activated in irradiated mouse lung tissues. The early application of STING inhibitor significantly alleviated radiation-induced inflammatory cell infiltration and pro-inflammatory cytokine release in lung tissue, as well as the degree of fibrosis in the late stage. The amount of double-stranded DNA (dsDNA) in the supernatant of irradiated MLE-12 cells was abnormally increased, and the epithelial-derived dsDNA could promote the transformation of fibroblasts into my...