Lipopolysaccharide induces physical proximity between CD14 and toll-like receptor 4 (TLR4) prior to nuclear translocation of NF-kappa B.
Lipopolysaccharide induces physical proximity between CD14 and toll-like receptor 4 (TLR4) prior to nuclear translocation of NF-kappa B.
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DOI：
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发表时间：
2000
影响因子：
4.4
通讯作者：
Q. Jiang;S. Akashi;K. Miyake;H. Petty
中科院分区：
文献类型：
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作者：
Q. Jiang;S. Akashi;K. Miyake;H. Petty
CD14是一种GPI连接蛋白，通过增强白细胞粘附、活化和细胞因子产生在LPS介导的信号传导中起关键作用。最近的研究已经确定Toll样受体4（TLR4）作为细胞因子诱导中LPS介导的跨膜信号转导的膜辅因子，尽管负责这种合作的机制尚不清楚。使用荧光共振能量转移（RET）技术，我们证明，LPS触发CD14和TLR4之间的物理关联。由于LPS刺激上调CD14和TLR4表达，因此有必要控制这些新表达的分子独立于LPS刺激而彼此相关的可能性。虽然钙离子载体A23187增加了CD14和TLR4的表达，但它们没有表现出能量转移。然而，在A23187处理后，LPS促进了CD14和TLR4之间的物理接近。因此，我们认为CD14和TLR4之间的密切相互作用参与LPS信号传导，导致NF-κ B的核转位。
CD14, a GPI-linked protein, plays a pivotal role in LPS-mediated signaling by potentiating leukocyte adherence, activation, and cytokine production. Recent studies have identified the Toll-like receptor 4 (TLR4) as a membrane cofactor in LPS-mediated transmembrane signaling in cytokine induction, although the mechanism responsible for this cooperation is unknown. Using fluorescence resonance energy transfer (RET) techniques, we demonstrate that LPS triggers a physical association between CD14 and TLR4. Because LPS stimulation upregulates CD14 and TLR4 expression, it was necessary to control for the possibility that these newly expressed molecules were associated with one another independent of LPS stimulation. Although the calcium ionophore A23187 increased the expression of CD14 and TLR4, they did not exhibit energy transfer. However, following A23187 treatment, LPS promoted physical proximity between CD14 and TLR4. Therefore, we suggest that a close interaction between CD14 and TLR4 participates in LPS signaling, leading to nuclear translocation of NF-kappaB.