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Kidney int:白细胞介素-6/Stat3信号在尿路感染中的重要作用!

2018-02-26 MedSci MedSci原创

调节泌尿道感染(UTI)期间抗菌活性的信号网络目前尚不完全清楚。白细胞介素-6(IL-6)水平随着UTI的严重程度而增加,但IL-6对宿主细菌性尿路致病原免疫的特异性作用仍然未知。为了澄清这一点,近期,一项发表在杂志Kidney int上的研究检测了IL-6是否激活Stat3转录因子,以驱动UTI期间感染的尿路上皮细胞中抗微生物肽基因表达的程序。经尿道接种尿道致病性大肠杆菌导致IL-6的分泌,尿路

调节泌尿道感染(UTI)期间抗菌活性的信号网络目前尚不完全清楚。白细胞介素-6(IL-6)水平随着UTI的严重程度而增加,但IL-6对宿主细菌性尿路致病原免疫的特异性作用仍然未知。

为了澄清这一点,近期,一项发表在杂志Kidney int上的研究检测了IL-6是否激活Stat3转录因子,以驱动UTI期间感染的尿路上皮细胞中抗微生物肽基因表达的程序。

经尿道接种尿道致病性大肠杆菌导致IL-6的分泌,尿路上皮Stat3磷酸化和抗微生物肽转录的活化(在小鼠膀胱炎模型中以Toll样受体4依赖性方式)。

在体外原代尿道上皮细胞中,重组IL-6可以引起Stat3的磷酸化,全身性予以IL-6促进体内尿路上皮Stat3磷酸化和抗微生物肽的表达。 IL-6缺陷导致UTI后尿路上皮Stat3磷酸化和抗微生物肽mRNA的表达降低,这一发现与条件性Stat3的缺失相反。

IL-6或Stat3的缺乏还与细胞内细菌群落的形成增加相关,并且外源性IL-6逆转了IL-6敲除小鼠中的这种表型。此外,慢性IL-6消耗导致C3H/HeOuJ小鼠肾细菌负荷增加以及严重的肾盂肾炎。

此项研究结果表明IL-6/Stat3信号传导驱动感染的尿路上皮细胞中抗微生物基因表达的转录程序,在限制上皮侵袭和上行感染中起关键作用。

原始出处:
Ching CB, Gupta S, et al. Interleukin-6/Stat3 signaling has an essential role in the host antimicrobial response to urinary tract infection. Kidney Int. 2018 Feb 20. pii: S0085-2538(18)30031-0. doi: 10.1016/j.kint.2017.12.006.

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    2018-02-28 李研东
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    2018-02-28 gwc389
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    2018-02-26 明月清辉

    谢谢分享.学习了

    0

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