Membrane-anchored CD14 is required for LPS-induced TLR4 endocytosis in TLR4/MD-2/CD14 overexpressing CHO cells
Membrane-anchored CD14 is required for LPS-induced TLR4 endocytosis in TLR4/MD-2/CD14 overexpressing CHO cells
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DOI：
10.1016/j.bbrc.2005.10.102
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发表时间：
2005-12-23
影响因子：
3.1
通讯作者：
Kai, H
中科院分区：
文献类型：
--
作者：
Shuto, T;Kato, K;Kai, H
脂多糖（LPS）通过TLR 4（toll样受体-4）/MD-2（髓样分化-2）/CD 14（分化簇-14）复合物诱导炎症活化。尽管需要最佳的LPS信号来激活我们的先天免疫系统对抗革兰氏阴性细菌，但过量的LPS信号在革兰氏阴性细菌感染中产生有害的炎症反应。表面TLR 4表达下调是限制LPS信号传导的关键机制之一。在此，我们发现膜锚定的CID 14是LPS诱导的CHO细胞中TLR 4和MD-2下调所必需的。此外，用甾醇结合剂filipin预处理细胞减少LPS诱导的TLR 4下调，表明小窝介导的内吞途径的参与。免疫沉淀进一步证实了小窝参与LPS诱导的TLR 4内吞作用。因此，我们的数据表明，小窝依赖的内吞途径参与LPS诱导的TLR 4下调，这是依赖于油膜锚定的CD 14表达。(c)2005年爱思唯尔公司All rights reserved.
Lipopolysaccharide (LPS) induces inflammatory activation through TLR4 (toll-like receptor-4)/MD-2 (myeloid differentiation-2)/CD14 (Cluster of differentiation-14) complex. Although optimal LPS signaling is required to activate our innate immune systems against gram-negative bacterium, excessive amount of LPS signaling develops a detrimental inflammatory response in gram-negative bacterial infections. Downregulation of surface TLR4 expression is one of the critical mechanisms that can restrict LPS signaling. Here, we found that membrane-anchored CID 14 is required for LPS-induced downregulation of TLR4 and MD-2 in CHO cells. Moreover, pretreatment of the cells with sterol-binding agent filipin reduced LPS-induced TLR4 downregulation, suggesting the involvement of caveolae-mediated endocytosis pathway. Involvement of caveolae in LPS-induced TLR4 endocytosis was further confirmed by immunoprecipitation. Thus, our data indicate that caveolac-dependent endocytosis pathway is involved in LPS-induced TLR4 downregulation and that this is dependent oil membrane-anchored CD14 expression. (c) 2005 Elsevier Inc. All rights reserved.