Heat-killed Salmonella typhimurium mitigated radiation-induced lung injury
Heat-killed Salmonella typhimurium mitigated radiation-induced lung injury
复制标题
热灭活鼠伤寒沙门氏菌减轻辐射引起的肺损伤
DOI：
10.1111/1440-1681.13135
复制
发表时间：
2019-12-01
影响因子：
2.9
通讯作者：
Yang Yanyong
中科院分区：
文献类型：
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作者：
Cao Kun;Luo Tao;Yang Yanyong
放射性肺损伤(RILI)是胸部肿瘤放射治疗的严重并发症。常见于临床胸部放射治疗和核事故或核武器攻击所致的急性全身照射。据报道，一些辐射防护剂在辐射暴露前给予会产生防护作用，然而，目前还没有预防RILI的治疗策略。在这项研究中，我们证明了热灭活鼠伤寒沙门氏菌(HKST)是Toll样受体2(TLR2)、Toll样受体4(TLR4)和Toll样受体5(TLR5)的共同激动剂，通过转化生长因子-β(TGF-β)信号通路减轻放射性肺损伤。我们发现，HKST可以减轻辐射后肺充血和病理损伤，表明HKST抑制了放射性肺损伤的早期炎症反应。在RILI的后期(7-14周)，我们首次观察到HKST减少了辐射诱导的胶原沉积，我们发现HKST抑制了辐射诱导的肺组织细胞凋亡。我们发现，HKST降低了转化生长因子-β的水平，并调节了其下游的信号通路。结果发现，HKST可抑制辐射诱导的肺组织上皮-间充质转化(EMT)。综上所述，我们的研究结果表明，HKST通过调节转化生长因子-β，有效地减轻了RILI，为全身放疗中RILI的治疗提供了新的策略。
Radiation-induced lung injury (RILI) is a serious complication in thoracic tumour radiotherapy. It often occurs in clinical chest radiotherapy and acute whole-body irradiation (WBI) caused by nuclear accidents or nuclear weapon attack. Some radioprotective agents have been reported to exert protective effects when given prior to radiation exposure, however, there is no treatment strategy available for preventing RILI. In this study, we demonstrated that heat-killed Salmonella typhimurium (HKST), a co-agonist of Toll-like receptors 2 (TLR2), Toll-like receptors 4 (TLR4) and Toll-like receptors 5 (TLR5), mitigated radiation-induced lung injury through the transforming growth factor-beta (TGF-beta) signalling pathway. We found that HKST alleviated lung hyperaemia and pathological damage after irradiation, indicated that HKST inhibits the early inflammatory reaction of radiation-induced lung injury. Then, for the first time, we observed HKST reduced collagen deposit induced by irradiation in the later phase (7-14 week) of RILI, and we found that HKST inhibited radiation-induced cell apoptosis in lung tissues. We found that HKST reduced the level of TGF-beta and regulated its downstream signalling pathway. Finally, it was found that HKST inhibited radiation-induced epithelial-mesenchymal transition (EMT) in lung tissues. In conclusion, our data showed that HKST effectively mitigated RILI through regulating TGF-beta, provide novel treatment strategy for RILI in whole-body irradiation and radiotherapy.