Inhibition of lipopolysaccharide activity by a bacterial cyclic lipopeptide surfactin
Inhibition of lipopolysaccharide activity by a bacterial cyclic lipopeptide surfactin
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DOI：
10.1038/ja.2006.6
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发表时间：
2006-01-01
影响因子：
3.3
通讯作者：
Umezawa, K
中科院分区：
文献类型：
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作者：
Takahashi, T;Ohno, O;Umezawa, K
灭活脂多糖活性的化合物具有成为新型抗炎药的潜力。因此，我们在微生物次级代谢物中寻找抑制lps刺激的人脐静脉内皮细胞（HUVEC）和HL-60细胞之间粘附的化合物。通过筛选，我们发现从芽孢杆菌BML752-121F2培养液中提取的环状脂肽表面素具有抑制作用。在LPS刺激之前加入表面素可以降低HL-60细胞的huvec粘附，但没有表现出任何细胞毒性。我们证实了表面素抑制lps诱导的HUVEC中ICAM-1和vcam -1的表达。抑制脂多糖活性成分脂质A诱导的细胞粘附；但不抑制tnf - α或IL-1 β诱导的细胞粘附。然后，表面素被证明抑制脂质A与LPS结合蛋白（LBP）的相互作用，LBP介导LPS向其受体的运输。最后，表面等离子体共振（SPR）分析显示，表面素与脂质a可逆相互作用，因此，该芽孢杆菌表面素被证明是LPS诱导的信号转导抑制剂，直接与LPS相互作用。
Compounds that inactivate lipopolysaceharide (LPS) activity have the potential of being new anti-inflammatory agents. Therefore, we searched among microbial secondary metabolites for compounds that inhibited LPS-stimulated adhesion between human umbilical vein endothelial cells (HUVEC) and HL-60 cells. By this screening, we found a cyclic lipopeptide surfactin from the Culture broth of Bacillus sp. BML752-121F2 to be inhibitory. The addition of the surfactin prior to the LPS stimulation decreased HL-60 cell-HUVEC adhesion Without showing any cytotoxicity. We confirmed that surfactin inhibited LPS-induced expression of ICAM-1 and VCAM-I in HUVEC. It also inhibited the cellular adhesion induced by lipid A, the active component of LPS; but it did not inhibit TNF-alpha or IL-1 beta-induced cell adhesion. Then, surfactin was shown to Suppress the interaction of lipid A with LPS-binding protein (LBP) that mediates the transport of LPS to its receptors. Finally, Surface plasmon resonance (SPR) analysis revealed the surfactin to interact reversibly with lipid A. Thus, this Bacillus surfactin was shown to be an inhibitor of LPS-induced signal transduction, directly interacting with LPS.