Cyanobacterial LPS antagonist (CyP)-a novel and efficient inhibitor of Escherichia coli LPS-induced cytokine response in the pig.
Cyanobacterial LPS antagonist (CyP)-a novel and efficient inhibitor of Escherichia coli LPS-induced cytokine response in the pig.
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DOI：
10.1016/j.molimm.2008.05.005
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发表时间：
2008-08
影响因子：
3.6
通讯作者：
E. Thorgersen;A. Macagno;C. Rossetti;T. Mollnes
中科院分区：
文献类型：
--
作者：
E. Thorgersen;A. Macagno;C. Rossetti;T. Mollnes
Toll样受体是先天免疫系统的必需模式识别受体。它们识别入侵微生物的一系列保守分子。先天性免疫系统被开发以保护宿主，但如果不受控制或不适当地激活，例如在革兰氏阴性细菌的败血症中，则可能是有害的。新的治疗方法，如抑制先天免疫反应，可能有利于这些条件的结果。与CD 14和MD-2相关的Toll样受体4是脂多糖（LPS）受体，并且是这种干预的候选者之一。我们研究了新描述的蓝藻LPS类似物CyP作为大肠杆菌（E. coli）的潜在抑制剂。coli）LPS诱导的猪全血中的炎症反应。使用促炎细胞因子和可溶性末端补体复合物sC 5 b-9作为读数。CyP与E. coli LPS，使用高达1μg/mL全血的剂量不诱导细胞因子产生，表明缺乏CyP的激动作用。CyP则是一种有效的LPS拮抗剂，可完全抑制E. coli LPS诱导TNF-α、IL-1β和IL-8的产生。与来自其他革兰氏阴性菌的LPS相比，CyP是猪补体的适度激活剂。当CyP在加入全E.大肠杆菌中，观察到对细胞因子的适度、可变和非显著抑制，对IL-1β的平均抑制达到44%。我们首次证明了蓝藻LPS类似物CyP是一种有效的大肠杆菌抑制剂。coli LPS诱导的全血细胞因子，可能是治疗性LPS抑制的候选者。
Toll-like receptors are essential pattern-recognition receptors of the innate immune system. They recognize a range of conserved molecules of invading microorganisms. The innate immune system is developed to protect the host, but can be deleterious if activated uncontrolled or inappropriate, such as in sepsis with Gram-negative bacteria. New approaches for treatment, like inhibition of innate immune responses, may be beneficial for the outcome of such conditions. Toll-like receptor 4 associated with CD14 and MD-2, is the lipopolysaccharide (LPS)-receptor and one of the candidates for such intervention. We investigated the newly described cyanobacterial LPS analogue CyP as a potential inhibitor of Escherichia coli (E. coli) LPS-induced inflammatory response in porcine whole blood. Pro-inflammatory cytokines and soluble terminal complement complex, sC5b-9, were used as read-outs. CyP, in contrast to E. coli LPS, did not induce cytokine production using doses up to 1μg/mL whole blood, indicating a lack of agonistic effect of CyP. In contrast, CyP was an efficient LPS antagonist, dose-dependently and completely inhibiting E. coli LPS-induced TNF-α, IL-1β and IL-8 production. CyP was a modest activator of porcine complement compared to LPS from other Gram-negative bacteria. When CyP was pre-incubated in porcine whole blood before adding whole E. coli bacteria, a modest, variable and non-significant inhibition of cytokines were seen, reaching an average inhibition of 44% for IL-1β. We have demonstrated for the first time that the cyanobacterial LPS analogue, CyP, is an efficient inhibitor of E. coli LPS-induced cytokines in whole blood and may be a candidate for therapeutic LPS-inhibition.