Shrimp (Penaeus monodon) anti-lipopolysaccharide factor reduces the lethality of Pseudomonas aeruginosa sepsis in mice
Shrimp (Penaeus monodon) anti-lipopolysaccharide factor reduces the lethality of Pseudomonas aeruginosa sepsis in mice
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DOI：
10.1016/j.intimp.2007.01.006
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发表时间：
2007-05-01
影响因子：
5.6
通讯作者：
Kuo, Ching-Ming
中科院分区：
文献类型：
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作者：
Pan, Chia-Yu;Chao, Tsung-Tai;Kuo, Ching-Ming
我们研究了合成的虾抗脂多糖因子肽（SALF（55-76）环肽）的氨基酸55-76的效力，所述氨基酸55- 76是虾抗脂多糖因子的C-末端部分。本研究旨在阐明这种肽的防腐作用的效果。SALF 55 -76环肽针对细菌临床分离株进行了测试，并显示出广谱抗微生物活性。SALF 55 -76环肽处理的铜绿假单胞菌的透射电子显微镜（TEM）检查显示，严重肿胀之前的细胞死亡和外膜的破裂;细胞内包涵体被发现已经流出细胞外。当在用铜绿假单胞菌进行细菌攻击之前用SALF 55 -76环肽处理小鼠时，该肽高度保护小鼠免于败血症死亡。4小时后从SALF 55 -76环肽处理的小鼠中回收的铜绿假单胞菌表现出与从万古霉素处理的小鼠中回收的相似的减少的细菌生长。另外。在SALF 55 -76环肽处理后4小时，除肝脏中的IL-4外，炎性细胞因子如白细胞介素（IL）-2，IL-4，IL-10，IL-12，IL-13，干扰素-γ和肿瘤坏死因子[TNF]-α的合成显著上调。Toll样受体4（Tlr 4）、Irf 3、myd 88和Tram的表达在SALF 55 -76环肽处理后4 h显著升高，但仅Tlr 4在脾脏中存在。通过ELISA分析，与未处理的小鼠相比，SALF 55 -76环肽的预防性施用开始TNF-α应答。由于其多功能特性，SALF 55 -76环肽可能成为预防和治疗细菌感染性疾病以及感染性休克的重要药物。(c)2007 Elsevier B. V.保留所有权利。
We investigated the efficacy of amino acids 55-76 of the synthetic shrimp anti-lipopolysaccharide factor peptide (SALF(55-76) cyclic peptide), the C-terminal part of the shrimp anti-lipopolysaccharide factor. This study was conducted to elucidate the effects of the antiseptic action of this peptide. The SALF55-76 Cyclic peptide was tested against bacterial clinical isolates and showed broad-spectrum antimicrobial activity. Transmission electron microscopic (TEM) examination of SALF55-76 cyclic peptide-treated Pseudomonas aeruginosa showed that severe swelling preceded cell death and breakage of the outer membrane; the intracellular inclusion was found to have effluxed extracellularly. When mice were treated with the SALF55-76 cyclic peptide before bacterial challenge with P. aeruginosa, the peptide highly protected mice against death by sepsis. The P. aeruginosa recovered from SALF55-76 cyclic peptide-treated mice after 4 h exhibited reduced bacterial growth similar to that recovered from vancomycin-treated mice. In addition. the syntheses of inflammatory cytokines, such as interleukin (IL)-2, IL-4, IL-10, IL-12, IL-13, interferon-gamma, and tumor necrosis factor [TNF]-alpha, were significantly upregulated 4 h after SALF55-76 cyclic peptide treatment except for IL-4 in the liver. The expressions of Toll-like receptor 4 (Tlr4), Irf3, myd88, and Tram, were considerably elevated, but only Tlr4 existed in the spleen 4 h after SALF55-76 cyclic peptide treatment. The prophylactic administration of SALF55-76 Cyclic peptide was begun the TNF-alpha response in comparison to untreated mice by an ELISA analysis. Due to its multifunctional properties, the SALF55-76 cyclic peptide may become an important prophylaxis against and therapy for bacterial infectious diseases, as well as for septic shock. (c) 2007 Elsevier B.V. All rights reserved.