Primary cilia modulate TLR4-mediated inflammatory responses in hippocampal neurons.
Primary cilia modulate TLR4-mediated inflammatory responses in hippocampal neurons.
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DOI：
10.1186/s12974-017-0958-7
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发表时间：
2017-09-19
影响因子：
9.3
通讯作者：
Kim DW
中科院分区：
文献类型：
--
作者：
Baek H;Shin HJ;Kim JJ;Shin N;Kim S;Yi MH;Zhang E;Hong J;Kang JW;Kim Y;Kim CS;Kim DW
初级纤毛是一种细胞器，可以充当细胞信号传导的主要调节器。尽管海马神经元中存在初级纤毛，但其功能尚未完全了解。最近的研究表明，初级纤毛影响白细胞介素（IL）-1β诱导的NF-κB信号，最终介导炎症反应。因此，我们结合纤毛长度分析研究了脂多糖（LPS）诱导的神经炎症中纤毛功能和NF-κB信号转导。由于TLR 4/NF-κB信号传导是一种众所周知的炎症通路，我们测量了注射LPS的野生型（WT）和TLR 4 −/−小鼠的纤毛长度和炎症介质。接下来，为了排除小胶质细胞TLR 4的影响，我们检查了HT 22海马神经元细胞中的纤毛长度、纤毛组分、炎性细胞因子和介质。侧脑室注射LPS后，WT小鼠海马锥体神经元的初级纤毛长度减少，而TLR 4 −/−小鼠的初级纤毛长度增加。LPS处理后HT 22海马神经元的初级纤毛长度减少，NF-κB信号激活，Cox 2和iNOS水平升高。相反，沉默Kif 3a，纤毛的关键蛋白组分，增加ARL 13 B纤毛蛋白水平，抑制NF-κB信号传导和炎症介质的表达。这些数据表明LPS诱导的NF-κB信号传导和炎症介质表达受纤毛调节，并且Kif 3a siRNA对初级纤毛形成的阻断调节TLR 4诱导的NF-κB信号传导。我们认为，初级纤毛是至关重要的调节NF-κB信号在神经炎症和先天性免疫反应的事件。本文的在线版本（10.1186/s12974-017-0958-7）包含补充材料，可供授权用户使用。
The primary cilium is an organelle that can act as a master regulator of cellular signaling. Despite the presence of primary cilia in hippocampal neurons, their function is not fully understood. Recent studies have demonstrated that the primary cilium influences interleukin (IL)-1β-induced NF-κB signaling, ultimately mediating the inflammatory response. We, therefore, investigated ciliary function and NF-κB signaling in lipopolysaccharide (LPS)-induced neuroinflammation in conjunction with ciliary length analysis. Since TLR4/NF-κB signaling is a well-known inflammatory pathway, we measured ciliary length and inflammatory mediators in wild type (WT) and TLR4−/− mice injected with LPS. Next, to exclude the effects of microglial TLR4, we examined the ciliary length, ciliary components, inflammatory cytokine, and mediators in HT22 hippocampal neuronal cells. Primary ciliary length decreased in hippocampal pyramidal neurons after intracerebroventricular injection of LPS in WT mice, whereas it increased in TLR4−/− mice. LPS treatment decreased primary ciliary length, activated NF-κB signaling, and increased Cox2 and iNOS levels in HT22 hippocampal neurons. In contrast, silencing Kif3a, a key protein component of cilia, increased ARL13B ciliary protein levels and suppressed NF-κB signaling and expression of inflammatory mediators. These data suggest that LPS-induced NF-κB signaling and inflammatory mediator expression are modulated by cilia and that the blockade of primary cilium formation by Kif3a siRNA regulates TLR4-induced NF-κB signaling. We propose that primary cilia are critical for regulating NF-κB signaling events in neuroinflammation and in the innate immune response. The online version of this article (10.1186/s12974-017-0958-7) contains supplementary material, which is available to authorized users.
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影响因子：
9.3
作者：
Leow-Dyke S;Allen C;Denes A;Nilsson O;Maysami S;Bowie AG;Rothwell NJ;Pinteaux E
通讯作者：
Pinteaux E
DOI：
10.1073/pnas.1210192110
发表时间：
2013-05-07
影响因子：
11.1
作者：
Berbari, Nicolas F.;Pasek, Raymond C.;Yoder, Bradley K.
通讯作者：
Yoder, Bradley K.
影响因子：
5.3
作者：
Lattke, Michael;Magnutzki, Alexander;Baumann, Bernd
通讯作者：
Baumann, Bernd
影响因子：
4.8
作者：
Guillot, L;Medjane, S;Si-Tahar, M
通讯作者：
Si-Tahar, M
影响因子：
64.5
作者：
Gerdes JM;Davis EE;Katsanis N
通讯作者：
Katsanis N