Early and preferential induction of IL-1 receptor-associated kinase-M in THP-1 cells by LPS derived from Porphyromonas gingivalis
Early and preferential induction of IL-1 receptor-associated kinase-M in THP-1 cells by LPS derived from Porphyromonas gingivalis
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DOI：
10.1189/jlb.0607432
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发表时间：
2008-03-01
影响因子：
5.5
通讯作者：
Yamazaki, Kazuhisa
中科院分区：
文献类型：
--
作者：
Domon, Hisanori;Honda, Tomoyuki;Yamazaki, Kazuhisa
牙龈卟啉单胞菌（P. gingivalis）的LPS被认为是牙周炎的毒力因子，刺激宿主细胞产生促炎介质。然而，据报道，牙龈卟啉单胞菌LPS与大肠杆菌（Escherichia coli，E. coli）LPS。虽然脂质A和赋予LPS信号传导的受体的化学结构的差异被认为是这些特征的原因，但确切的原因尚不清楚。在此，我们证明牙龈卟啉单胞菌LPS在THP-1衍生的巨噬细胞中比E. coli LPS。虽然小干扰（si）RNA下调IRAK-M增强了LPS刺激的巨噬细胞中TNF-α、IL-6和IL-12 p40的转录和翻译，但siRNA的作用在牙龈卟啉单胞菌LPS刺激的细胞中更为突出。IRAK-1在E.大肠杆菌LPS刺激的巨噬细胞比用牙龈卟啉单胞菌LPS刺激的细胞更易诱导IRAK-M，表明牙龈卟啉单胞菌LPS诱导的IRAK-M抑制IRAK-1从受体复合物的解离，导致从随后的降解中逃逸。这种活性可能参与牙周组织中这种细菌的慢性感染，作为逃避免疫监视的机制。
LPS of Porphyromonas gingivalis (P. gingivalis) is suggested to be a virulence factor in periodontitis, stimulating host cells to produce proinflammatory mediators. However, P. gingivalis LPS has been reported to show lower biological activity compared with Escherichia coli ( E. coli) LPS. Although differences in the chemical structure of lipid A and the receptor conferring LPS signaling are thought to account for these characteristics, the precise reason is unknown. Here, we demonstrate that P. gingivalis LPS up-regulates IL-1R-associated kinase (IRAK)-M, a negative regulator of the TLR signaling pathway, in a THP-1derived macrophage more robustly than E. coli LPS. Although down-regulation of IRAK-M by small interfering ( si) RNA augmented transcription and translation of TNF-alpha, IL-6, and IL-12 p40 in LPS-stimulated macrophages, the effect of siRNA was more prominent in P. gingivalis LPS-stimulated cells. Degradation of IRAK-1 was more obvious in E. coli LPS-stimulated macrophages than the cells stimulated with P. gingivalis LPS, suggesting that P. gingivalis LPS-induced IRAK-M suppressed dissociation of IRAK-1 from the receptor complex, resulting in escape from subsequent degradation. This activity may be involved in the chronic infection of this bacterium in periodontal tissue by serving as an escape mechanism from immune surveillance.