Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2
Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2
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DOI：
10.1074/jbc.274.25.17406
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发表时间：
1999-06-18
影响因子：
4.8
通讯作者：
Kirschning, CJ
中科院分区：
文献类型：
--
作者：
Schwandner, R;Dziarski, R;Kirschning, CJ
革兰氏阴性菌和革兰氏阳性菌感染引起的脓毒症是人类危及生命的并发症。最近，脂多糖（LPS），革兰氏阴性菌的主要生物活性剂，被证明介导细胞活化的人Toll样受体家族的成员，Toll样受体（TLR）2。本文研究了革兰氏阳性菌的主要刺激成分可溶性肽聚糖（sPGN）和脂磷壁酸（LTA）激活细胞的机制。与LPS一样，sPGN和LTA与糖基磷脂酰肌醇锚定的膜蛋白CD 14结合，并诱导宿主细胞如巨噬细胞中转录因子NF-κ B B的激活。我们发现，整个革兰氏阳性菌，sPGN和LTA诱导NF-κ B B在HEK 293细胞表达TLR 2的激活，但不表达TLR 1或TLR 4的细胞。多粘菌素B（一种结合并中和LPS的抗生素）不抑制sPGN和LTA诱导的NF-κ B B活化。与膜CD 14共表达增强sPGN通过TLR 2的信号传递。与LPS信号传导相反，sPGN和LTA对TLR 2的激活不需要血清。这些发现表明TLR 2除了LPS之外还可以作为sPGN和LTA的信号传导器。
The Life-threatening complications of sepsis in humans are elicited by infection with Gram-negative as well as Gram-positive bacteria. Recently, lipopolysaccharide (LPS), a major biologically active agent of Gram-negative bacteria, was shown to mediate cellular activation by a member of the human Toll-like receptor family, Toll-like receptor (TLR) 2. Here we investigate the mechanism of cellular activation by soluble peptidoglycan (sPGN) and lipoteichoic acid (LTA), main stimulatory components of Gram-positive bacteria, Like LPS, sPGN and LTA bind to the glycosylphosphatidylinositol-anchored membrane protein CD14 and induce activation of the transcription factor NF-kappa B in host cells like macrophages. We show that whole Gram-positive bacteria, sPGN and LTA induce the activation of NF-kappa B in HEK293 cells expressing TLR2 but not in cells expressing TLR1 or TLR4. The sPGN- and LTA-induced NF-kappa B activation was not inhibited by polymyxin B, an antibiotic that binds and neutralizes LPS. Coexpression together with membrane CD14 enhances sPGN signal transmission through TLR2. In contrast to LPS signaling, activation of TLR2 by sPGN and LTA does not require serum. These findings identify TLR2 as a signal transducer for sPGN and LTA in addition to LPS.