Establishment of S100A8 Transgenic Rats to Understand Innate Property of S100A8 and Its Immunological Role
Establishment of S100A8 Transgenic Rats to Understand Innate Property of S100A8 and Its Immunological Role
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DOI：
10.1007/s10753-017-0664-8
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发表时间：
2018-02-01
期刊：
影响因子：
5.1
通讯作者：
Ikemoto, Masaki
中科院分区：
文献类型：
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作者：
Okada, Kohki;Itoh, Hiroshi;Ikemoto, Masaki
S100 A8作为急性炎症调节因子的固有特性尚未详细阐明。本研究的目的是建立S100 A8转基因大鼠（Tg-S100 A8），并研究S100 A8的免疫学功能。在用5%葡聚糖硫酸钠治疗1周后，Tg-S100 A8的体重在开始后轻微下降，然而，日本Wistar大鼠（WT）的体重在最后显著下降。Tg-S100 A8组血清CRP水平显著低于WT组，但Tg-S100 A8组和WT组血清CRP水平均显著升高。免疫荧光染色观察巨噬细胞中S100 A8和S100 A9的动态迁移，发现S100 A9主要表达于WT直肠组织的巨噬细胞中。通过PCR和实时定量PCR检测，Tg-S100 A8的几个器官组织如心脏和小肠中的S100 A8信使RNA（mRNA）的水平分别明显高于WT。Tg-S100 A8大肠主要器官组织中IL-6和TNF-α mRNA表达呈负调控，随后IL-6蛋白表达下调。一个重要的结果是，在许多Tg-S100 A8巨噬细胞中，S100 A8 mRNA的表达被强烈诱导，而上述一些炎性细胞因子mRNA的表达显著降低。Tg-S100 A8具有作为有用的实验模型大鼠的潜力，不仅用于研究S100 A8作为调节剂的固有特性，而且用于阐明其在来自骨髓来源的免疫细胞，特别是巨噬细胞中的功能作用。
The innate properties of S100A8 as a regulator in acute inflammation have not yet been elucidated in detail. Our aims are to newly establish S100A8 transgenic rats (Tg-S100A8) and to elucidate the immunological functions of S100A8. Following the treatment with 5% dextran sulfate sodium for 1 week, the body weight in Tg-S100A8 weakly decreased after the start; however, that in Japanese Wistar rats (WT) significantly decreased in the end. The serum level of CRP in Tg-S100A8 was significantly lower than that in WT, although the concentration of CRP apparently increased in both Tg-S100A8 and WT. The dynamic mobility of S100A8 and S100A9 in macrophages was microscopically observed using fluorescent immunological staining, in which the S100A9 was dominantly expressed in many macrophages in the rectal tissue of WT. As determined by PCR and real-time PCR, the levels of S100A8 messenger RNA (mRNA) in several organ tissues of the Tg-S100A8, such as heart and small intestine, were apparently higher than those of WT, respectively. The expression of IL-6 and TNF-alpha mRNAs was negatively regulated in main organ tissues of the large colon of Tg-S100A8 followed by down-regulation of IL-6 protein. An important result was that the expression of S100A8 mRNA was strongly induced in many macrophages of Tg-S100A8, whereas that of some inflammatory cytokine mRNAs described above were significantly reduced. Tg-S100A8 has potential as a useful experimental model rat not only for investigating the innate properties of S100A8 as a regulator, but also for clarifying its functional role in immune cells from a myeloid origin, particularly macrophages.