LPS response and tolerance in the zebrafish (Danio rerio).

LPS response and tolerance in the zebrafish (Danio rerio).
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DOI:
10.1016/j.fsi.2008.12.004
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发表时间:
2009-02
影响因子:
4.7
通讯作者:
Figueras A
Figueras A
中科院分区:
农林科学2区
文献类型:
--
作者:
Novoa B;Bowman TV;Zon L;Figueras A

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以斑马鱼(Danio rerio)为实验材料,研究了斑马鱼对细菌脂多糖(LPS)暴露的反应和LPS耐受性。这些机制在哺乳动物中尚未完全了解,目前在鱼类中也完全未知。在用各种浓度的各种类型的LPS处理后评估斑马鱼幼虫的存活,以确定斑马鱼对LPS诱导的免疫激活的敏感性。此外,用亚致死浓度的LPS预处理的鱼在暴露于致死浓度的LPS后没有死亡,这首次证明LPS耐受性也发生在鱼中。预处理和二次暴露之间的时间间隔以及预处理的类型决定了保护的强度。由于斑马鱼与微生物密切接触,鱼类对LPS的高抗性表明必须严格控制LPS受体簇,以避免过度炎症。其中一种成分是CXCR4,它以前被证明可以调节TLR4转导的信号。用AMD 3100(CXCR4的特异性抑制剂)处理鱼增加了LPS处理相关的死亡率。通过化学或遗传抑制阻断CXCR4导致LPS耐受性逆转,从而进一步支持CXCR4在这种炎症反应中的负调节作用。在炎症级联反应中CXCR4的抑制作用的支持,IL 1转录水平升高,在未刺激和LPS刺激的斑马鱼Odysseus(CXCR4缺陷突变体)幼虫。
Zebrafish (Danio rerio) has been used in the present work to study the fish response to bacterial lipopolysaccharide (LPS) exposure and LPS tolerance. These mechanisms are not completely understood in mammals and, presently, are totally unknown in fish. Zebrafish larval survival was assessed following treatment with various types of LPS at a variety of concentrations to determine the sensitivity of zebrafish to LPS-induced immune activation. In addition, fish pre-treated with a sublethal concentration of LPS did not die after exposure to a lethal concentration of LPS demonstrating, for the first time, that LPS tolerance also happens in fish. The time interval between pretreatment and secondary exposure as well as the type of pretreatment dictated the strength of protection. Since zebrafish are in intimate contact with microorganisms, the high resistance of fish to LPS suggests that there must be a tight control of the LPS receptor cluster in order to avoid an excess of inflammation. One of these components is CXCR4, which has previously been shown to regulate the signal transduced by TLR4. Treating fish with AMD 3100, a specific inhibitor of CXCR4, increased LPS treatment associated mortality. Blocking CXCR4 via chemical or genetic inhibition resulted in a reversion of LPS tolerance, thus further supporting the negative regulatory role of CXCR4 in this inflammatory response. In support of an inhibitory role for CXCR4 in the inflammatory cascade, IL1 transcript levels were elevated in both unstimulated and LPS stimulated zebrafish Odysseus (CXCR4 deficient mutant) larvae.
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