Heat-killed salmonella typhimurium (HKST) protects mice against radiation in TLR4-dependent manner.
Heat-killed salmonella typhimurium (HKST) protects mice against radiation in TLR4-dependent manner.
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热灭活的鼠伤寒沙门氏菌 (HKST) 以 TLR4 依赖性方式保护小鼠免受辐射
DOI：
10.18632/oncotarget.17859
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发表时间：
2017-09-15
期刊：
影响因子：
--
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Xu Y;Chen Y;Liu H;Lei X;Guo J;Cao K;Liu C;Li B;Cai J;Ju J;Gao F;Yang Y
因此，迫切需要开发新型、安全、有效的辐射防护剂来减轻辐射损伤。近年来，研究发现，Toll样受体（TLRs）包括TLR2、TLR4、TLR5、TLR9等，具有抗电离辐射的作用。由于不同的组织分布和不同的功能的TLR，我们假设，同时共激活多个TLR可能会产生广泛的和更强的辐射防护作用。本研究发现，TLR2、TLR4和TLR5共激动剂热灭活鼠伤寒沙门氏菌（HKST）能显著抑制辐射诱导的细胞凋亡，提高细胞存活率，减轻DNA损伤。HKST还能延长动物的存活时间，并保护对辐射敏感的组织免受辐射损伤，如骨髓、脾脏和睾丸。CD4+和CD8+细胞的减少也被HKST逆转。利用TLR2和TLR4基因敲除小鼠，我们发现HKST的大部分辐射防护作用在TLR4基因敲除小鼠中被取消。HKST不能抑制TLR5基因敲减细胞的凋亡。总之，我们证明HKST有效地保护细胞和辐射敏感组织免受TLR4偏置机制的辐射损伤，这表明HKST是一种潜在的低毒性辐射防护剂。
It is urgently required to develop novel safe and effective radioprotectors to alleviate radiation damages. Recently, several toll like receptors (TLRs), including TLR2, TLR4, TLR5, TLR9, have been proved to exert protective effects against ionizing radiation. Due to different tissue-distribution and distinct functions of TLRs, we hypothesized that co-activation of multiple TLRs simultaneously may produce extensive and stronger radioprotective effects. In this study, we found the co-agonist of TLR2, TLR4 and TLR5, heat-killed salmonella typhimurium (HKST) significantly inhibited radiation-induced cell apoptosis, increased cell survival and alleviated DNA damage. HKST also prolonged animal survival and protected radiosensitive tissues against radiation damages, such as bone marrow, spleen and testis. Decrease of CD4+ and CD8+ cells were also reversed by HKST treatment. By using TLR2 and TLR4 knockout mice, we found that most of radioprotective effects of HKST were abrogated in TLR4 knock out mice. And HKST failed to inhibited cell apoptosis in TLR5 knock down cells. In conclusion, we demonstrated that HKST effectively protected cells and radiosensitive tissues against radiation injury in a TLR4 biased mechanism, suggesting HKST as a potential radioprotector with low toxicity.
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DOI：
10.1016/j.ijrobp.2003.09.028
发表时间：
2004-02-01
影响因子：
7
作者：
Olive, PL;Banáth, JP
通讯作者：
Banáth, JP
影响因子：
9
作者：
通讯作者：
--
全身照射后给予小鼠 CpG 寡脱氧核苷酸对骨髓造血的辐射保护
影响因子：
2
作者：
Zhang, Chao;Lin, Jing;Cai, Jianming
通讯作者：
Cai, Jianming
影响因子：
5.7
作者：
Borgmann, K;Röper, B;Dahm-Daphi, J
通讯作者：
Dahm-Daphi, J
影响因子：
5.8
作者：
Citrin, Deborah;Cotrim, Ana P.;Mitchell, James B.
通讯作者：
Mitchell, James B.