A critical role of toll-like receptor 4 (TLR4) and its' in vivo ligands in basal radio-resistance.
A critical role of toll-like receptor 4 (TLR4) and its' in vivo ligands in basal radio-resistance.
复制标题
DOI：
10.1038/cddis.2013.161
复制
发表时间：
2013-05-30
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
Toll 样受体 4 (TLR4) 在先天性和获得性免疫中发挥着关键作用，但其在放射抗性中的作用尚不清楚。我们使用TLR4敲除（KO，−/−）小鼠和肠道共生耗竭方法，来测试TLR4及其体内激动剂对基础放射抗性的影响。我们发现，TLR4 缺陷的小鼠更容易受到 IR 诱导的死亡率和发病率的影响。 IR后TLR4缺陷小鼠的死亡率与严重且持续的骨髓细胞损失有关。将脂多糖注射到正常小鼠体内，已知会激活体内的 TLR4，从而诱导放射抗性。此外，TLR4 体内配体是基础放射抗性所必需的。我们发现暴露于辐射会导致显着的内毒素血症，这也赋予了免受辐射的内源性保护。循环内毒素似乎源自肠道，因为用抗生素对肠道进行消毒会导致辐射死亡率增加。进一步的数据表明，Myd88（而非 TRIF）可能是 TLR4 诱导的放射抗性中的关键接头。总而言之，这些数据强烈表明 TLR4 在基础放射抗性中发挥着关键作用。我们的数据表明，在全身照射之前不要给予可能对肠道进行消毒的抗生素，这一点很重要。此外，这些数据还表明，通过抗生素或可能的益生菌疗法管理肠道菌群可能会改变对全身照射的先天反应。
Toll-like receptor-4 (TLR4) plays a critical role in innate and acquired immunity, but its role in radio-resistance is unknown. We used TLR4 knockout (KO,−/−) mice and gut commensal depletion methods, to test the influence of TLR4 and its' in vivo agonist on basal radio-resistance. We found that mice deficient in TLR4 were more susceptible to IR-induced mortality and morbidity. Mortality of TLR4-deficient mice after IR was associated with a severe and persistent bone marrow cell loss. Injection of lipopolysaccharide into normal mice, which is known to activate TLR4 in vivo, induced radio-resistance. Moreover, TLR4 in vivo ligands are required for basal radio-resistance. We found that exposure to radiation leads to significant endotoxemia that also confers endogenous protection from irradiation. The circulating endotoxins appear to originate from the gut, as sterilization of the gut with antibiotics lead to increased mortality from radiation. Further data indicated that Myd88, but not TRIF, may be the critical adaptor in TLR4-induced radio-resistance. Taken together, these data strongly suggest that TLR4 plays a critical role in basal radio-resistance. Our data suggest, it is important not to give antibiotics that may sterilize the gut before the whole body irradiation. Further, these data also suggest that management of gut flora through antibiotic or possibly probiotic therapy may alter the innate response to the total body irradiation.
登录
查看更多内容
影响因子：
2
作者：
Yamamoto M;Takeda K
通讯作者：
Takeda K
伽马射线照射通过下调 CCR7 和诱导细胞凋亡来损害树突状细胞向 CCL19 的迁移
影响因子：
9.2
作者：
Liu C;Lin J;Zhao L;Yang Y;Gao F;Li B;Cui J;Cai J
通讯作者：
Cai J
影响因子：
56.9
作者：
Fagarasan, S;Muramatsu, M;Honjo, T
通讯作者：
Honjo, T
影响因子：
7.4
作者：
Lee, JH;Park, JW
通讯作者：
Park, JW
DOI：
10.1038/nri1957
发表时间：
2006-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Marshak-Rothstein A
通讯作者：
Marshak-Rothstein A