Radiation upregulates macrophage TREM-1 expression to exacerbate injury in mice.
Radiation upregulates macrophage TREM-1 expression to exacerbate injury in mice.
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DOI：
10.3389/fimmu.2023.1151250
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
暴露于高剂量电离辐射会导致组织损伤、感染，甚至因免疫功能障碍而死亡。髓样细胞上表达的触发受体-1（TREM-1）已被证明严重放大和失调免疫应答。然而，TREM-1在辐射损伤中的作用仍然未知。细胞外冷诱导RNA结合蛋白（eCIRP）是一种新的损伤相关分子模式，在炎症过程中由激活或应激的细胞释放。我们假设电离辐射通过eCIRP释放上调TREM-1表达，使从C57 BL/6野生型（WT）小鼠收集的RAW 264. 7细胞和腹腔巨噬细胞的存活率恶化，这些细胞和腹腔巨噬细胞暴露于5-和10-Gray（戈伊）辐射。C57 BL/6 WT和CIRP-/-小鼠经历10-戈伊全身照射（TBI）。流式细胞术检测RAW264.7细胞和腹腔巨噬细胞TREM-1的表达。通过蛋白质印迹法评估从辐射小鼠分离的细胞培养上清液和腹膜灌洗液中的eCIRP水平。我们还评估了6.5-戈伊TBI后C57 BL/6 WT、CIRP-/-和TREM-1-/-小鼠的30天存活率。5-和10-戈伊照射后24 h，RAW 264. 7细胞表面TREM-1蛋白和mRNA水平显著升高。TREM-1在腹腔巨噬细胞上的表达在体外和体内辐射暴露后显著增加。在体外和体内腹腔灌洗中，在腹膜巨噬细胞的细胞培养上清液中的eCIRP水平在辐射暴露后显著增加。此外，与WT小鼠相比，CIRP-/-小鼠在6.5-戈伊TBI后表现出增加的存活率。有趣的是，在10-戈伊TBI后24小时，与WT小鼠相比，CIRP-/-小鼠中腹膜巨噬细胞上的TREM-1表达显著降低。此外，在6.5-戈伊TBI后，TREM-1-/-小鼠的30天存活率显著增加至64%，而WT小鼠为20%。我们的数据表明，电离辐射通过释放eCIRP增加巨噬细胞中的TREM-1表达，并且TREM-1导致全身照射后的生存率更差。因此，靶向TREM-1有可能被开发为辐射损伤的新医学对策。
Exposure to high-dose ionizing radiation causes tissue injury, infections and even death due to immune dysfunction. The triggering receptor expressed on myeloid cells-1 (TREM-1) has been demonstrated to critically amplify and dysregulate immune responses. However, the role of TREM-1 in radiation injury remains unknown. Extracellular cold-inducible RNA-binding protein (eCIRP), a new damage-associated molecular pattern, is released from activated or stressed cells during inflammation. We hypothesized that ionizing radiation upregulates TREM-1 expression via eCIRP release to worsen survival RAW264.7 cells and peritoneal macrophages collected from C57BL/6 wild-type (WT) mice were exposed to 5- and 10-Gray (Gy) radiation. C57BL/6 WT and CIRP-/- mice underwent 10-Gy total body irradiation (TBI). TREM-1 expression on RAW264.7 cells and peritoneal macrophages in vitro and in vivo were evaluated by flow cytometry. eCIRP levels in cell culture supernatants and in peritoneal lavage isolated from irradiated mice were evaluated by Western blotting. We also evaluated 30-day survival in C57BL/6 WT, CIRP-/- and TREM-1-/- mice after 6.5-Gy TBI. The surface protein and mRNA levels of TREM-1 in RAW264.7 cells were significantly increased at 24 h after 5- and 10-Gy radiation exposure. TREM-1 expression on peritoneal macrophages was significantly increased after radiation exposure in vitro and in vivo. eCIRP levels were significantly increased after radiation exposure in cell culture supernatants of peritoneal macrophages in vitro and in peritoneal lavage in vivo. Moreover, CIRP-/- mice exhibited increased survival after 6.5-Gy TBI compared to WT mice. Interestingly, TREM-1 expression on peritoneal macrophages in CIRP-/- mice was significantly decreased compared to that in WT mice at 24 h after 10-Gy TBI. Furthermore, 30-day survival in TREM-1-/- mice was significantly increased to 64% compared to 20% in WT mice after 6.5-Gy TBI. Our data indicate that ionizing radiation increases TREM-1 expression in macrophages via the release of eCIRP, and TREM-1 contributes to worse survival after total body irradiation. Thus, targeting TREM-1 could have the potential to be developed as a novel medical countermeasure for radiation injury.
影响因子：
3.3
作者：
Sun W;Liao Y;Yi Q;Wu S;Tang L;Tong L
通讯作者：
Tong L