Differential induction of endotoxin tolerance by lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli
Differential induction of endotoxin tolerance by lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli
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DOI：
10.4049/jimmunol.167.9.5278
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发表时间：
2001-11-01
影响因子：
4.4
通讯作者：
Michalek, SM
中科院分区：
文献类型：
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作者：
Martin, M;Katz, J;Michalek, SM
单核吞噬细胞暴露于肠细菌 LPS 会导致对随后的 LPS 暴露产生短暂的低反应状态，称为内毒素耐受。在本研究中，比较了源自口腔牙周病原体牙龈卟啉单胞菌的脂多糖与源自肠杆菌大肠杆菌的脂多糖诱导内毒素耐受的能力。用大肠杆菌 LPS 预处理人巨噬细胞系 THP-1 后，二次刺激后可导致 IL-1β、IL-6 和 TNF-α 水平严重降低。相比之下，用牙龈卟啉单胞菌LPS预处理THP-1细胞导致IL-1β的减少，但在随后暴露于小于或等于100ng/ml牙龈卟啉单胞菌LPS的初次或二次刺激时，IL-6和TNF-α的产生没有减少，导致IL-6和TNF-α的水平相当，而用 大于或等于 1 微克/毫升的牙龈卟啉单胞菌 LPS 在二次暴露后诱导 IL-6 和 TNF-α 水平显着增强。为了确定这些差异的可能机制，评估了 LPS 信号通路中涉及的分子表达的变化。用大肠杆菌 LPS 预处理 THP-1 细胞，导致表面 Toll 样受体 4 (TLR4) 表达显着减少，并且在二次刺激时无法降解 I-kappaB-α 或 I-kappaB-β 蛋白。相比之下，用牙龈卟啉单胞菌LPS预处理THP-1细胞导致CD14和TLR2显着增强，同时保持仅在二次刺激时降解I-κB-β的能力。因此，大肠杆菌和牙龈卟啉单胞菌 LPS 对 CD14 和 TLR 表达以及次级 LPS 相关反应有不同的影响。
Exposure of mononuclear phagocytes to enterobacterial LPS induces a state of transient hyporesponsiveness to subsequent LPS exposure, termed endotoxin tolerance. In the present study, LPS derived from the oral periodontal pathogen, Porphyromonas gingivalis, was compared with that derived from the enterobacterium, Escherichia coli, for the ability to induce endotoxin tolerance. Pretreatment of the human macrophage cell line, THP-1, with E. coli LPS resulted in a severe reduction in the levels of IL-1 beta, IL-6, and TNF-alpha upon secondary stimulation. In contrast, pretreatment of THP-1 cells with P. gingivalis LPS resulted in a mitigation of IL-1 beta, but not IL-6 and TNF-alpha production upon subsequent exposure to P. gingivalis LPS primary or secondary stimulation with less than or equal to 100 ng/ml P. gingivalis LPS resulted in comparable levels of IL-6 and TNF-alpha, while stimulation of THP-1 cells with greater than or equal to1 mug/ml P. gingivalis LPS induced a significant enhancement in IL-6 and TNF-alpha levels upon secondary exposure. To identify possible mechanisms for these differences, changes in the expression of molecules involved in the LPS-signaling pathway were assessed. Pretreatment of THP-1 cells with E. coli LPS resulted in a significant reduction in surface Toll-like receptor 4 (TLR4) expression and an inability to degrade I-kappaB-alpha or I-kappaB-beta proteins upon secondary stimulation. In contrast, pretreatment of THP-1 cells with P. gingivalis LPS resulted in a significant enhancement of both CD14 and TLR2, while maintaining the ability to degrade I-kappaB-beta only upon secondary stimulation. Thus, E. coli and P. gingivalis LPS differentially affect CD14 and TLR expression as well as secondary LPS-associated responses.