Co-operation of TLR4 and raft proteins in LPS-induced pro-inflammatory signaling.
Co-operation of TLR4 and raft proteins in LPS-induced pro-inflammatory signaling.
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DOI：
10.1007/s00018-014-1762-5
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发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Kwiatkowska K
中科院分区：
文献类型：
--
作者：
Płóciennikowska A;Hromada-Judycka A;Borzęcka K;Kwiatkowska K
Toll样受体4(TLR4)是由革兰氏阴性细菌的一种成分脂多糖(LPS)激活的，目的是诱导促炎介质的产生，以根除细菌。宿主对内毒素的反应失调可导致全身炎症，称为脓毒症。在一个典型的场景中，TLR4的激活之前，内毒素与CD14蛋白结合，CD14蛋白锚定在质膜的富含胆固醇和鞘磷脂的微域中，称为RAFT。然后CD14将内毒素转移到TLR4/MD-2复合体，TLR4/MD-2复合体二聚化并触发依赖于MyD88和TRIF的促炎细胞因子和I型干扰素的产生。依赖于TRIF的信号与激活的TLR4的内吞作用有关，TLR4由CD14控制。除CD14外，其他RAFT蛋白如Src家族的Lyn酪氨酸激酶、酸性鞘磷脂酶、CD44、Hsp70和CD36等也参与了由内毒素和非微生物内源性配体触发的TLR4信号转导。本文就RAFT参与TLR4信号转导的研究现状进行综述，重点介绍RAFT蛋白如何调控TLR4信号转导途径。带有CD14的木筏，以及可能富含CD36的木筏，被认为是介导激活的TLR4内吞的多分子复合体的首选组装部位。
Toll-like receptor 4 (TLR4) is activated by lipopolysaccharide (LPS), a component of Gram-negative bacteria to induce production of pro-inflammatory mediators aiming at eradication of the bacteria. Dysregulation of the host responses to LPS can lead to a systemic inflammatory condition named sepsis. In a typical scenario, activation of TLR4 is preceded by binding of LPS to CD14 protein anchored in cholesterol- and sphingolipid-rich microdomains of the plasma membrane called rafts. CD14 then transfers the LPS to the TLR4/MD-2 complex which dimerizes and triggers MyD88- and TRIF-dependent production of pro-inflammatory cytokines and type I interferons. The TRIF-dependent signaling is linked with endocytosis of the activated TLR4, which is controlled by CD14. In addition to CD14, other raft proteins like Lyn tyrosine kinase of the Src family, acid sphingomyelinase, CD44, Hsp70, and CD36 participate in the TLR4 signaling triggered by LPS and non-microbial endogenous ligands. In this review, we summarize the current state of the knowledge on the involvement of rafts in TLR4 signaling, with an emphasis on how the raft proteins regulate the TLR4 signaling pathways. CD14-bearing rafts, and possibly CD36-rich rafts, are believed to be preferred sites of the assembly of a multimolecular complex which mediates the endocytosis of activated TLR4.
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影响因子：
5.1
作者：
Bzowska, Malgorzata;Nogiec, Anna;Skrzeczynska-Moncznik, Joanna;Mickowska, Barbara;Guzik, Krzysztof;Pryjma, Juliusz
通讯作者：
Pryjma, Juliusz
影响因子：
3.5
作者：
Benting, J;Rietveld, A;Simons, K
通讯作者：
Simons, K
影响因子：
4.8
作者：
Chiang, Chih-Yuan;Veckman, Ville;David, Michael
通讯作者：
David, Michael
影响因子：
4.4
作者：
Aneja, Rajesh;Odoms, Kelli;Wong, Hector R.
通讯作者：
Wong, Hector R.
影响因子：
2
作者：
Cuschieri, Joseph;Bulger, Eileen;Maier, Ronald V
通讯作者：
Maier, Ronald V