Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells.
Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells.
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Toll样受体4位于高尔基体中，并与肠上皮细胞中的内部脂多糖共定位。
DOI：
10.1084/jem.20011788
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发表时间：
2002-03-04
期刊：
影响因子：
--
通讯作者：
Richter-Dahlfors A
中科院分区：
文献类型：
--
作者：
Hornef MW;Frisan T;Vandewalle A;Normark S;Richter-Dahlfors A
Toll样受体（TLR）4主要存在于骨髓造血谱系的细胞上。它识别脂多糖（LPS）并介导细胞活化和促炎细胞因子的产生。对TLR 4在持续暴露于微生物和微生物产物的上皮细胞中的分布和作用知之甚少。在这里，我们表明，小鼠小肠上皮细胞系m-ICcl 2是高度响应LPS和表达CD 14和TLR 4。LPS暴露后，CD 14的转录和表面膜染色上调。令人惊讶的是，TLR 4免疫染色显示严格的细胞质旁核分布。这个核旁区室可以被鉴定为高尔基体。加入到上清液中的LPS被m-ICcl 2细胞内化并与TLR 4共定位。连续暴露于LPS导致耐受表型，但不改变TLR 4表达或细胞分布。因此，肠上皮细胞可能能够提供最初的促炎信号，以吸引专业免疫细胞到感染侧。TLR 4的胞质定位与内化LPS的最终定位相同，进一步表明细胞内化和胞质运输在先天免疫识别过程中的重要作用。
Toll-like receptor (TLR) 4 is mainly found on cells of the myelopoietic lineage. It recognizes lipopolysaccharide (LPS) and mediates cellular activation and production of proinflammatory cytokines. Less is known about the distribution and role of TLR4 in epithelial cells that are continuously exposed to microbes and microbial products. Here we show that the murine small intestinal epithelial cell line m-ICcl2 is highly responsive to LPS and expresses both CD14 and TLR4. Transcription and surface membrane staining for CD14 were up-regulated upon LPS exposure. Surprisingly, TLR4 immunostaining revealed a strictly cytoplasmic paranuclear distribution. This paranuclear compartment could be identified as the Golgi apparatus. LPS added to the supernatant was internalized by m-ICcl2 cells and colocalized with TLR4. Continuous exposure to LPS led to a tolerant phenotype but did not alter TLR4 expression nor cellular distribution. Thus, intestinal epithelial cells might be able to provide the initial proinflammatory signal to attract professional immune cells to the side of infection. The cytoplasmic location of TLR4, which is identical to the final location of internalized LPS, further indicates an important role of cellular internalization and cytoplasmic traffic in the process of innate immune recognition.
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